TÍTULO / TITLE: - Alzheimer’s Disease and Down Syndrome Rodent Models Exhibit Audiogenic Seizures.
RESUMEN / SUMMARY:
-
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REVISTA / JOURNAL:
- J Alzheimers Dis. 2010 Apr 22.
AUTORES / AUTHORS:
- Westmark CJ; Westmark PR; Malter JS
INSTITUCIÓN / INSTITUTION:
- Department of Pathology & Laboratory Medicine and Waisman Center for Developmental Disabilities, University of Wisconsin, Madison, WI, USA.
RESUMEN / SUMMARY:
- Amyloid-beta protein precursor (AbetaPP) is overexpressed in Alzheimer’s disease (AD), Down syndrome (DS), autism, and fragile X syndrome. Seizures are a common phenotype in all of these neurological disorders, yet the underlying molecular mechanism(s) of seizure induction and propagation remain largely unknown. We demonstrate that AD (Tg2576) and DS (Ts65Dn) mice exhibit audiogenic seizures, which can be attenuated with antagonists to metabotropic glutamate receptor 5 (mGluR{5}) or by passive immunization with anti-amyloid-beta antibody. Our data strongly implicates AbetaPP or a catabolite in seizure susceptibility and suggests that mGluR{5} mediates this response.
TÍTULO / TITLE:
- Discovery of Cyclic Acylguanidines as Highly Potent and Selective beta-Site Amyloid Cleaving Enzyme (BACE) Inhibitors: Part I-Inhibitor Design and Validation
RESUMEN / SUMMARY:
REVISTA / JOURNAL:
- JOURNAL OF MEDICINAL CHEMISTRY, 53 (3): 951-965 FEB 11 2010
AUTORES / AUTHORS:
- Zhu, ZN; Sun, ZY; Ye, YZ; Voigt, J; Strickland, C; Smith, EM; Cumming, J; Wang, LY; Wong, J; Wang, YS; Wyss, DF; Chen, X; Kuvelkar, R; Kennedy, ME; Fa
RESUMEN / SUMMARY:
- A number of novel amidine containing heterocycles were designed to reproduce the unique interaction pattern, revealed by X-ray crystallography, between the BACE-1 catalytic diad and a weak NMR screening hit (3), with special attention paid to maintaining the appropriate basicity and limiting the number of H-bonding donors of these scaffolds. The iminohydantoin cores (10 and 23) were examined first and found to interact with the catalytic diad in one of two binding modes (A and B), each with the iminohydantoin core flipped 180 degrees in relation to the other. The amidine structural motif within each core forms a bidentate interaction with a different aspartic acid of the catalytic diad. Both modes reproduced a highly conserved interaction pattern between the inhibitors and the catalytic aspartates, as revealed by 3. Potent iminohydantoin BACE-1 inhibitors have been obtained, validating the molecular design as aspartyl protease catalytic site inhibitors. Brain penetrant sm! all molecule BACE inhibitors with high ligand efficiencies have been discovered, enabling multiple strategies for further development of these inhibitors into highly potent, selective and in vivo efficacious BACE inhibitors.
TÍTULO / TITLE:
- Down syndrome and aging: a leadership and social justice landscape.
RESUMEN / SUMMARY:
-
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REVISTA / JOURNAL:
- J Cult Divers. 2010 Spring;17(1):34-8.
AUTORES / AUTHORS:
- Nevel KM
INSTITUCIÓN / INSTITUTION:
- Alvernia College, 1930 Squire Court, Wyomissing, PA 19610, USA.
kathleennevel@gmail.com
RESUMEN / SUMMARY:
- The growing phenomenon of aging adults with Down syndrome and other intellectual and developmental disabilities and dementia can be traumatic and overwhelming for families and caregivers. The realization is beset with angst and necessitates restructuring policies and programs while exploring the leadership landscape to facilitate a values framework for persons with Down syndrome. This article considers the changing role of the caregiver and the influences of community support networks, social policy, social justice, and quality of life adaptations for aging persons with Down syndrome and dementia. Note: To maintain confidentiality, personal communications noted throughout this article identify the individual using initials rather than surname.
TÍTULO / TITLE:
- Dyrk1A-mediated phosphorylation of Presenilin 1: a functional link between Down syndrome and Alzheimer’s disease.
RESUMEN / SUMMARY:
-
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REVISTA / JOURNAL:
- J Neurochem. 2010 Apr 23.
AUTORES / AUTHORS:
- Ryu YS; Park SY; Jung MS; Yoon SH; Kwen MY; Lee SY; Choi SH; Radnaabazar C; Kim MK; Kim H; Kim K; Song WJ; Chung SH
INSTITUCIÓN / INSTITUTION:
- Graduate Program in Neuroscience, Institute for Brain Science and Technology (IBST), Inje University, Busan, South Korea.
RESUMEN / SUMMARY:
- J. Neurochem. (2010) 10.1111/j.1471-4159.2010.06769.x Abstract The dual-specificity tyrosine(Y)-phosphorylation-regulated kinase 1ª (Dyrk1A) gene is located on human chromosome 21 and encodes a proline-directed protein kinase that might be responsible for mental retardation and early onset of Alzheimer’s disease (AD) in Down syndrome (DS) patients. Presenilin 1 (PS1) is a key component of the gamma-secretase complex in the generation of beta-amyloid (Abeta), an important trigger protein in the pathogenesis of AD. Increased Dyrk1A expression has been reported in human AD and DS brains. We previously showed that Dyrk1A increased Abeta production in mammalian cells and transgenic mice that over-express Dyrk1A. In this study, we describe a potential mechanism by which Abeta is increased in Dyrk1A-over-expressing DS and AD brains. First, we show that PS1 is phosphorylated by the Dyrk1A at Thr(354) and that this phosphorylation increases gamma-secretase activity. Then, using transgenic mice that over-express human Dyrk1A, we demonstrate that phospho-Thr354-PS1 (pT354-PS1) expression is enhanced when Dyrk1A level is increased. We also show that pT354-PS1 is more stable than the unphosphorylated form of PS1. These results reveal a potential regulatory link between Dyrk1A and PS1 in the Abeta pathway of DS and AD brains, suggesting that up-regulated Dyrk1A may accelerate AD pathogenesis through PS1 phosphorylation.
TÍTULO / TITLE:
- Memantine Normalizes Several Phenotypic Features in the Ts65Dn Mouse Model of Down Syndrome.
RESUMEN / SUMMARY:
-
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REVISTA / JOURNAL:
- J Alzheimers Dis. 2010 Apr 26.
AUTORES / AUTHORS:
- Rueda N; Llorens-Martin M; Florez J; Valdizan E; Banerjee P; Trejo JL; Martinez-Cue C
INSTITUCIÓN / INSTITUTION:
- Department of Physiology and Pharmacology, Faculty of Medicine, University of Cantabria, Santander, España.
RESUMEN / SUMMARY:
- Ts65Dn (TS) mice exhibit several phenotypic characteristics of human Down syndrome, including an increased brain expression of amyloid-beta protein precursor (AbetaPP) and cognitive disturbances. Aberrant N-methyl-D-aspartate (NMDA) receptor signaling has been suspected in TS mice, due to an impaired generation of hippocampal long-term potentiation (LTP). Memantine, an uncompetitive NMDA receptor antagonist approved for the treatment of moderate to severe Alzheimer’s disease, is known to normalize LTP and improve cognition in transgenic mice with high brain levels of AbetaPP and amyloid-beta protein. It has recently been demonstrated that acute injections of memantine rescue performance deficits of TS mice on a fear conditioning test. Here we show that oral treatment of aged TS mice with a clinically relevant dose of memantine (30 mg/kg/day for 9 weeks) improved spatial learning in the water maze task and slightly reduced brain AbetaPP levels. We also found that TS mice exhibited a significantly reduced granule cell count and vesicular glutamate transporter-1 (VGLUT1) labeling compared to disomic control mice. After memantine treatment, the levels of hippocampal VGLUT1 were significantly increased, reaching the levels observed in vehicle treated-control animals. Memantine did not significantly affect granule cell density. These data indicate that memantine may normalize several phenotypic abnormalities in TS mice, many of which - such as impaired cognition - are also associated with Down syndrome and Alzheimer’s disease.
TÍTULO / TITLE:
- Alzheimer’s disease amyloid-beta links lens and brain pathology in Down syndrome.
RESUMEN / SUMMARY:
-
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REVISTA / JOURNAL:
- PLoS One. 2010 May 20;5(5):e10659.
AUTORES / AUTHORS:
- Moncaster JA; Pineda R; Moir RD; Lu S; Burton MA; Ghosh JG; Ericsson M; Soscia SJ; Mocofanescu A; Folkerth RD; Robb RM; Kuszak JR; Clark JI; Tanzi RE;
INSTITUCIÓN / INSTITUTION:
- Molecular Aging & Development Laboratory, Department of Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
RESUMEN / SUMMARY:
- Down syndrome (DS, trisomy 21) is the most common chromosomal disorder and the leading genetic cause of intellectual disability in humans. In DS, triplication of chromosome 21 invariably includes the APP gene (21q21) encoding the Alzheimer’s disease (AD) amyloid precursor protein (APP). Triplication of the APP gene accelerates APP expression leading to cerebral accumulation of APP-derived amyloid-beta peptides (Abeta), early-onset AD neuropathology, and age-dependent cognitive sequelae. The DS phenotype complex also includes distinctive early-onset cerulean cataracts of unknown etiology. Previously, we reported increased Abeta accumulation, co-localizing amyloid pathology, and disease-linked supranuclear cataracts in the ocular lenses of subjects with AD. Here, we investigate the hypothesis that related AD-linked Abeta pathology underlies the distinctive lens phenotype associated with DS. Ophthalmological examinations of DS subjects were correlated with phenotypic, histochemical, and biochemical analyses of lenses obtained from DS, AD, and normal control subjects. Evaluation of DS lenses revealed a characteristic pattern of supranuclear opacification accompanied by accelerated supranuclear Abeta accumulation, co-localizing amyloid pathology, and fiber cell cytoplasmic Abeta aggregates (approximately 5 to 50 nm) identical to the lens pathology identified in AD. Peptide sequencing, immunoblot analysis, and ELISA confirmed the identity and increased accumulation of Abeta in DS lenses. Incubation of synthetic Abeta with human lens protein promoted protein aggregation, amyloid formation, and light scattering that recapitulated the molecular pathology and clinical features observed in DS lenses. These results establish the genetic etiology of the distinctive lens phenotype in DS and identify the molecular origin and pathogenic mechanism by which lens pathology is expressed in this common chromosomal disorder. Moreover, these findings confirm increased Abeta accumulation as a key pathogenic determinant linking lens and brain pathology in both DS and AD.
TÍTULO / TITLE:
- Systemic Mitochondrial Dysfunction and the Etiology of Alzheimer’s Disease and Down Syndrome Dementia.
RESUMEN / SUMMARY:
-
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REVISTA / JOURNAL:
- J Alzheimers Dis. 2010 May 12.
AUTORES / AUTHORS:
- Coskun PE; Wyrembak J; Derbereva O; Melkonian G; Doran E; Lott IT; Head E; Cotman CW; Wallace DC
INSTITUCIÓN / INSTITUTION:
- Mitochondrial and Molecular Medicine and Genetics (MAMMAG), University of California Irvine, Irvine, CA, USA Department of Biological Chemistry, University of California Irvine, Irvine, CA, USA.
RESUMEN / SUMMARY:
- Increasing evidence is implicating mitochondrial dysfunction as a central factor in the etiology of Alzheimer’s disease (AD). The most significant risk factor in AD is advanced age and an important neuropathological correlate of AD is the deposition of amyloid-beta peptide (Abeta{40} and Abeta{42}) in the brain. An AD-like dementia is also common in older individuals with Down syndrome (DS), though with a much earlier onset. We have shown that somatic mitochondrial DNA (mtDNA) control region (CR) mutations accumulate with age in post-mitotic tissues including the brain and that the level of mtDNA mutations is markedly elevated in the brains of AD patients. The elevated mtDNA CR mutations in AD brains are associated with a reduction in the mtDNA copy number and in the mtDNA L-strand transcript levels. We now show that mtDNA CR mutations increase with age in control brains; that they are markedly elevated in the brains of AD and DS and dementia (DSAD) patients; and that the increased mtDNA CR mutation rate in DSAD brains is associated with reduced mtDNA copy number and L-strand transcripts. The increased mtDNA CR mutation rate is also seen in peripheral blood DNA and in lymphoblastoid cell DNAs of AD and DSAD patients, and distinctive somatic mtDNA mutations, often at high heteroplasmy levels, are seen in AD and DSAD brain and blood cells DNA. In aging, DS, and DSAD, the mtDNA mutation level is positively correlated with beta-secretase activity and mtDNA copy number is inversely correlated with insoluble Abeta{40} and Abeta{42} levels. Therefore, mtDNA alterations may be responsible for both age-related dementia and the associated neuropathological changes observed in AD and DSAD.
TÍTULO / TITLE:
- Optimization protocol for amyloid-beta peptides detection in human cerebrospinal fluid using SELDI TOF MS
RESUMEN / SUMMARY:
REVISTA / JOURNAL:
- PROTEOMICS CLINICAL APPLICATIONS, 4 (3): 352-357 MAR 2010
AUTORES / AUTHORS:
- Albertini, V; Bruno, A; Paterlini, A; Lista, S; Benussi, L; Cereda, C; Binetti, G; Ghidoni, R
RESUMEN / SUMMARY:
- Purpose: The aim of the present work was to set up an optimized protocol for human cerebrospinal fluid amyloid-beta (A beta) profiling.
Experimental design: We devised an immunoproteomic assay that employs monoclonal antibodies (mAbs) on Preactivated Surface (PS20) chip array followed by SELDI TOF MS. A comparison of a number of factors was performed, and the impact of these differences was noted. Each variable was tested using in parallel two different mAbs, 6E10 and 4G8. In addition, we tested whether the combined use of these two mAbs could improve the capture of N and C-terminally truncated A beta peptides and then the quality of spectra.
Results: The best results were obtained using a mixture of A beta mAbs (0.125 mu g/mu L 6E10+4G8): 15 A beta peptides (including 3 N-terminally truncated forms) were detected.
Conclusions and clinical relevance: This approach has many potential advantages in speed, sensitivity and economy of reagents and could be helpful in order to define the role played by specific A beta truncated forms in cognitive decline.
TÍTULO / TITLE:
- Age-related changes in plasma levels of BDNF in Down syndrome patients.
RESUMEN / SUMMARY:
-
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REVISTA / JOURNAL:
- Immun Ageing. 2010 Jan 25;7:2.
AUTORES / AUTHORS:
- Dogliotti G; Galliera E; Licastro F; Corsi MM
INSTITUCIÓN / INSTITUTION:
- Department of Human Morphology and Biomedical Sciences “Citta Studi”, Laboratory of Clinical Pathology, University of Milan, Milan, Italy.
mmcorsi@unimi.it
RESUMEN / SUMMARY:
- ABSTRACT: BACKGROUND: The prevalence of coronary artery diseases is low among Down Syndrome (DS) patients and they rarely die of atherosclerotic complications. Histopathological investigations showed no increase in atherosclerosis, or even a total lack of atherosclerotic changes, in DS AIM: The aim of our study is to investigate the relationship between age and brain-derived neurotrophic factor (BDNF) levels in Down Syndrome (DS). SUBJECTS AND METHODS: Three groups of DS patients were studied: the first consisted of 23 children (age 2-14 years); the second of 14 adults (age 20-50 years), the third group of 13 elderly persons (>60 years) and a controls group of 20 healthy patients (age 15-60 years).The analytes of interest were quantified using a biochip array analyzer (Evidence®, Randox Ltd., Crumlin, UK). RESULTS: Plasma BDNF was higher in DS patients than in controls and there was a significant age-related increase. Serum levels of IL-6 and MCP-1 were also higher in DS children and adults, but not in older patients, than in healthy control. High levels of circulating BDNF may protect DS patients from the clinical complications of atherosclerosis. However, the striking drop in peripheral BDNF levels with age might predispose these patients to clinical manifestations of dementia in later life.
TÍTULO / TITLE:
- Theoretical exploration of the neural bases of behavioural disinhibition, apathy and executive dysfunction in preclinical Alzheimer’s disease in people with Down’s syndrome: potential involvement of m
RESUMEN / SUMMARY:
-
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REVISTA / JOURNAL:
- J Intellect Disabil Res. 2010 Feb 25.
AUTORES / AUTHORS:
- Ball SL; Holland AJ; Watson PC; Huppert FA
INSTITUCIÓN / INSTITUTION:
- University of Cambridge, Department of Psychiatry, Cambridge Intellectual & Developmental Disabilities Research Group, Cambridge, UK.
RESUMEN / SUMMARY:
- Abstract Background Recent research has suggested a specific impairment in frontal-lobe functioning in the preclinical stages of Alzheimer’s disease (AD) in people with Down’s syndrome (DS), characterised by prominent changes in personality or behaviour. The aim of the current paper is to explore whether particular kinds of change (namely executive dysfunction (EDF), disinhibition and apathy), associated in the literature with disruption of different underlying frontal-subcortical circuits, are a) more or less frequently reported than others and b) related to poor performance on tasks involving different cognitive processes. Method Seventy-eight participants (mean age 47 years, range 36-72) with DS and mild to moderate intellectual disability (based on ICD-10 criteria), without a diagnosis of dementia of Alzheimer’s type (DAT) or other psychiatric disorders, were selected from a larger sample of older adults with DS (n = 122). Dementia diagnosis was based on the CAMDEX informant interview, conducted with each participant’s main carer. Informant-reported changes in personality/behaviour and memory were recorded. Participants were scored based on symptoms falling into three behavioural domains and completed five executive function (EF) tasks, six memory tasks (two of which also had a strong executive component) and the BPVS (as a measure of general intellectual ability). Multiple regression analyses were conducted to determine the degree to which the behavioural variables of ‘EDF’, ‘disinhibition’ and ‘apathy’, along with informant-reported memory decline and antidepressant medication use, predicted performance on the cognitive tasks (whilst controlling for the effects of age and general intellectual ability). Results Strikingly, disinhibited behaviour was reported for 95.7% of participants with one or more behavioural change (n = 47) compared to 57.4% with reported apathy and 36.2% with reported EDF. ‘Disinhibition’ score significantly predicted performance on three EF tasks (designed to measure planning, response inhibition and working memory) and an object memory task, (also thought to place high demands on working memory), while ‘apathy’ score significantly predicted performance on two different tasks, those measuring spatial reversal and prospective memory (p < 0.05). Informant reported memory decline was associated only with performance on a delayed recall task while antidepressant medication use was associated with better performance on a working memory task (p < 0.05). Conclusion Observed dissociation between performance on cognitive tasks associated with reported apathy and disinhibition is in keeping with proposed differences underlying neural circuitry and supports the involvement of multiple frontal-subcortical circuits in the early stages of DAT in DS. However, the prominence of disinhibition in the behavioural profile (which more closely resembles that of disinhibited subtype of DFT than that of AD in the general population) leads us to postulate that the serotonergically mediated orbitofrontal circuit may be disproportionately affected. A speculative theory is developed regarding the biological basis for observed changes and discussion is focused on how this understanding may aid us in the development of treatments directly targeting underlying abnormalities.
TÍTULO / TITLE:
- Alzheimer`s-related endosome dysfunction in Down syndrome is A beta-independent but requires APP and is reversed by BACE-1 inhibition
RESUMEN / SUMMARY:
REVISTA / JOURNAL:
- PROC NAT ACAD SCI USA 107 (4): 1630-1635 JAN 26 2010
AUTORES / AUTHORS:
- Jiang, Y; Mullaney, KA; Peterhoff, CM; Che, SL; Schmidt, SD; Boyer-Boiteau, A; Ginsberg, SD; Cataldo, AM; Mathews, PM; Nixon, RA
RESUMEN / SUMMARY:
- An additional copy of the beta-amyloid precursor protein (APP) gene causes early-onset Alzheimer`s disease (AD) in trisomy 21 (DS). Endosome dysfunction develops very early in DS and AD and has been implicated in the mechanism of neurodegeneration. Here, we show that morphological and functional endocytic abnormalities in fibroblasts from individuals with DS are reversed by lowering the expression of APP or beta-APP-cleaving enzyme 1 (BACE-1) using short hairpin RNA constructs. By contrast, endosomal pathology can be induced in normal disomic (2N) fibroblasts by overexpressing APP or the C-terminal APP fragment generated by BACE-1 (beta CTF), all of which elevate the levels of beta CTFs. Expression of a mutant form of APP that cannot undergo beta-cleavage had no effect on endosomes. Pharmacological inhibition of APP gamma-secretase, which markedly reduced A beta production but raised beta CTF levels, also induced AD-like endosome dysfunction in 2N fibroblasts and worsened! this pathology in DS fibroblasts. These findings strongly implicate APP and the beta CTF of APP, and excludeA beta and the alpha CTF, as the cause of endocytic pathway dysfunction in DS and AD, underscoring the potential multifaceted value of BACE-1 inhibition in AD therapeutics.
TÍTULO / TITLE:
- Truncated {beta}-amyloid peptide channels provide an alternative mechanism for Alzheimer’s Disease and Down syndrome.
RESUMEN / SUMMARY:
-
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REVISTA / JOURNAL:
- Proc Natl Acad Sci U S A. 2010 Mar 22.
AUTORES / AUTHORS:
- Jang H; Arce FT; Ramachandran S; Capone R; Azimova R; Kagan BL; Nussinov R; Lal R
INSTITUCIÓN / INSTITUTION:
- Center for Cancer Research Nanobiology Program, SAIC-Frederick, Inc., National Cancer Institute, Frederick, MD 21702.
RESUMEN / SUMMARY:
- Full-length amyloid beta peptides (Abeta(1-40/42)) form neuritic amyloid plaques in Alzheimer’s disease (AD) patients and are implicated in AD pathology. However, recent transgenic animal models cast doubt on their direct role in AD pathology. Nonamyloidogenic truncated amyloid-beta fragments (Abeta(11-42) and Abeta(17-42)) are also found in amyloid plaques of AD and in the preamyloid lesions of Down syndrome, a model system for early-onset AD study. Very little is known about the structure and activity of these smaller peptides, although they could be the primary AD and Down syndrome pathological agents. Using complementary techniques of molecular dynamics simulations, atomic force microscopy, channel conductance measurements, calcium imaging, neuritic degeneration, and cell death assays, we show that nonamyloidogenic Abeta(9-42) and Abeta(17-42) peptides form ion channels with loosely attached subunits and elicit single-channel conductances. The subunits appear mobile, suggesting insertion of small oligomers, followed by dynamic channel assembly and dissociation. These channels allow calcium uptake in amyloid precursor protein-deficient cells. The channel mediated calcium uptake induces neurite degeneration in human cortical neurons. Channel conductance, calcium uptake, and neurite degeneration are selectively inhibited by zinc, a blocker of amyloid ion channel activity. Thus, truncated Abeta fragments could account for undefined roles played by full length Abetas and provide a unique mechanism of AD and Down syndrome pathologies. The toxicity of nonamyloidogenic peptides via an ion channel mechanism necessitates a reevaluation of the current therapeutic approaches targeting the nonamyloidogenic pathway as avenue for AD treatment.
TÍTULO / TITLE:
- Oligomeric A beta in Alzheimer`s Disease: Relationship to Plaque and Tangle Pathology, APOE Genotype and Cerebral Amyloid Angiopathy
RESUMEN / SUMMARY:
REVISTA / JOURNAL:
- BRAIN PATHOLOGY, 20 (2): 468-480 MAR 2010
AUTORES / AUTHORS:
- van Helmond, Z; Miners, JS; Kehoe, PG; Love, S
RESUMEN / SUMMARY:
- Despite accumulating evidence of a central role for oligomeric amyloid beta (A beta) in the pathogenesis of Alzheimer`s Disease (AD), there is scant information on the relationship between the levels and distribution of oligomeric A beta and those of other neurodegenerative abnormalities in AD. In the present study, we have found oligomeric A beta to be associated with both diffuse and neuritic plaques (mostly co-localized with A beta(1-42)) and with cerebrovascular deposits of A beta in paraffin sections of formalin-fixed human brain tissue. The amount of oligomeric A beta that was labeled in the sections correlated with total A beta plaque load, but not phospho-tau load, cerebral amyloid angiopathy (CAA) severity or APOE genotype. Although soluble, oligomeric and insoluble A beta levels were all significantly increased in AD brain homogenates, case-to-case variation and overlap between AD and controls were considerable. Over the age-range studied (43-98 years), the leve! ls of soluble A beta, oligomeric A beta(42), oligomeric A beta(40) and insoluble A beta did not vary significantly with age. Oligomeric A beta(1-42) and insoluble A beta levels were significantly higher in women. Overall, the level of insoluble A beta, but neither oligomeric nor soluble A beta, was associated with Braak stage, CAA severity and APOE epsilon 4 frequency, raising questions as to the role of soluble and oligomeric A beta in the progression of AD.
TÍTULO / TITLE:
- Autonomic response to upright tilt in people with and without Down syndrome.
RESUMEN / SUMMARY:
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REVISTA / JOURNAL:
- Res Dev Disabil. 2010 Mar 20.
AUTORES / AUTHORS:
- Agiovlasitis S; Collier SR; Baynard T; Echols GH; Goulopoulou S; Figueroa A; Beets MW; Pitetti KH; Fernhall B
INSTITUCIÓN / INSTITUTION:
- Department of Kinesiology, Mississippi State University, 233 McCarthy Gym, P.O. Box 6186, Mississippi State, MS 39762, USA.
RESUMEN / SUMMARY:
- This study examined whether the autonomic response to passive upright tilt as evidenced by changes in measures of heart rate and blood pressure variability differs between individuals with DS and without DS. Beat-to-beat blood pressure was measured in 26 individuals with Down syndrome (DS) and 11 individuals without DS during 5min of rest and 5min of upright tilt. Dependent variables included heart rate, blood pressure, frequency component measures of heart rate and blood pressure variability, and baroreflex sensitivity. The normalized high frequency (HF) power, normalized low frequency (LF) power, and LF/HF of heart rate variability, as well as the LF of blood pressure variability were reduced in persons with DS in response to upright tilt (p<0.05). This was accompanied by smaller change in baroreflex sensitivity (p<0.05) in individuals with DS. Blood pressure responses to upright tilt were also reduced in individuals with DS (p<0.05), but the heart rate response did not differ between groups. Individuals with DS show less vagal withdrawal and sympatho-excitation in response to passive upright tilt. These effects may be partially mediated by smaller change in baroreflex sensitivity in individuals with DS. The results support the hypothesis of altered autonomic modulation in people with DS.
TÍTULO / TITLE:
- Adults with Down syndrome: safety and long-term outcome of cardiac operation.
RESUMEN / SUMMARY:
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REVISTA / JOURNAL:
- Congenit Heart Dis. 2010 Jan;5(1):38-43.
AUTORES / AUTHORS:
- Majdalany DS; Burkhart HM; Connolly HM; Abel MD; Dearani JA; Warnes CA; Schaff HV
INSTITUCIÓN / INSTITUTION:
- Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN 55905, USA.
majdalany.david@mayo.edu
RESUMEN / SUMMARY:
- OBJECTIVE: As limited data exist, we sought to review the safety and outcome of cardiac surgery in the adult Down syndrome population. DESIGN: We reviewed the data of all patients >or=18 years old with Down syndrome who underwent cardiac surgery (1969-2008) at our hospital. RESULTS: Fifty patients underwent 57 surgeries (mean age 33 years). Fifteen patients had prior cardiac operations in childhood: 7 complete and 1 partial atrioventricular canal, 2 secundum atrial septal defect, 2 Tetralogy of Fallot, 1 patent ductus arteriosus, 1 combined atrioventricular canal and Tetralogy of Fallot, and 1 ventricular septal defect. Operations in adult Down syndrome patients included repair of partial atrioventricular canal in 17, aortic valve replacement in 7, mitral valve replacement/repair in 7, ventricular septal defect in 6, atrial septal defect in 3, Tetralogy of Fallot in 3, pulmonary valve replacement in 3, and other in 11. There was 1 in-hospital death (1.8%) from multiorgan failure. The mean hospital stay was 10.6 days. Average ventilatory support was 2.4 days (range 0-32). Atrial arrhythmias occurred in 14 patients (25%). Six patients had early postoperative pulmonary infections. Mean follow-up was 6 years, maximum 29 years. There were eight late deaths at an average age of 52 years (range 30-58) occurring 15 years postoperatively (range 32 days-29 years); two in the setting of dementia (mean age 56 years). CONCLUSION: At an experienced center, adult patients with Down syndrome can undergo cardiac surgery with a low risk of mortality and acceptable morbidity. Atrial arrhythmias and pulmonary infections are common postoperatively.
TÍTULO / TITLE:
- Congenital cardiovascular lesions in children with trisomy 21 at the Bustamante Hospital for Children.
RESUMEN / SUMMARY:
-
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REVISTA / JOURNAL:
- Cardiol Young. 2010 Mar 22:1-5.
AUTORES / AUTHORS:
- Tomlinson TW; Scott CH; Trotman HL
INSTITUCIÓN / INSTITUTION:
- 1Bustamante Hospital for Children, Arthur Wint Drive, Kingston 5, Jamaica.
RESUMEN / SUMMARY:
- OBJECTIVE: To describe the cardiac lesions seen in children with trisomy 21, the outcome of these children and rates of access to corrective surgery at the Bustamante Hospital for Children. METHODS: A 10-year retrospective review of the records of trisomy 21 patients with cardiac lesions referred to the Bustamante Hospital for Children was conducted. RESULTS: A total of 76 patients were enrolled in the study, 30 (40%) males and 46 (60%) females; among these 110 cardiac lesions were detected. A total of 20 (26%) patients died, 48 (63%) survived, and for 8 (11%) the status was unknown. The most common lesion was the atrioventricular septal defect, which accounted for 41 (37%) of all the lesions and occurred as a single defect in 24 (53%) patients. At presentation, 33 (46%) patients had one or more medical complication; 30 (91%) had cardiac failure, 10 (30%) had pneumonia and 5 (15%) had evidence of systemic pulmonary arterial pressures. Cardiac catheterisation was recommended for 43 (56%) patients but only 10 (23%) had the procedure done. Surgery was recommended for 60 (79%) patients; of these 6 (10%) patients had the procedure done. The median time of survival was 88 months (7.3 years). The age of presentation was not found to significantly affect outcome.ConclusionTrisomy 21 patients with cardiac lesions have high morbidity and mortality. This morbidity and mortality could be reduced if surgical intervention was offered routinely.
TÍTULO / TITLE:
- Heart rate recovery after exercise in adults with the Down syndrome.
RESUMEN / SUMMARY:
-
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REVISTA / JOURNAL:
- Am J Cardiol. 2010 May 15;105(10):1470-3. Epub 2010 Mar 30.
AUTORES / AUTHORS:
- Mendonca GV; Pereira FD
INSTITUCIÓN / INSTITUTION:
- Center of Human Performance, Faculty of Human Kinetics, Technical University of Lisbon, Lisbon, Portugal.
gvmendonca@gmail.com
RESUMEN / SUMMARY:
- The main purpose of this study was to evaluate heart rate recovery (HRR) in patients with the Down syndrome (DS) after peak dynamic exercise and compare their responses to those of nondisabled subjects of similar age, gender, and body mass index. Eighteen participants with the DS (14 men, 4 women; mean age 33.6 +/- 7.6 years) and 18 nondisabled controls (14 men, 4 women; mean age 33.8 +/- 8.5 years) performed peak treadmill tests with metabolic and heart rate measurements. Compared to controls, subjects with the DS presented lower peak values of heart rate, oxygen uptake, and minute ventilation (p <0.05). In contrast, the 2 groups attained similar respiratory exchange ratio values at peak exercise. Even after controlling for the effects of reduced peak heart rate and body mass index, participants with the DS showed slower HRR than controls at 1 minute (DS: 25.3 +/- 7.2 beats/min; controls: 34.1 +/- 12.1 beats/min) and 2 minutes (DS: 36.3 +/- 5.8 beats/min; controls: 53.6 +/- 14.1 beats/min) of recovery (p <0.05). In conclusion, adults with the DS had reduced HRR (at 1 and 2 minutes of recovery) compared to nondisabled controls, and this was independent of their lower chronotropic response to peak exercise. Additionally, despite showing attenuated HRR from peak exercise, adults with the DS did not present increased cardiovascular risk by general diagnostic criteria (HRR >12 and 22 beats/min, respectively).
TÍTULO / TITLE:
- The Heart Rate Response to Spontaneous Arousal from Sleep is Reduced in Children with Down Syndrome Referred for Evaluation of Sleep Disordered Breathing.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- Am J Physiol Heart Circ Physiol. 2010 Mar 26.
AUTORES / AUTHORS:
- O’Driscoll DM; Horne R; Davey MJ; Hope SA; Walker AM; Nixon GM
INSTITUCIÓN / INSTITUTION:
- 1Monash University.
RESUMEN / SUMMARY:
- Arousal from sleep in healthy adults is associated with a large, transient increase in heart rate (HR). Individuals with Down Syndrome (DS) have attenuated cardiovascular responses to autonomic tests during wakefulness. We tested the hypothesis that the HR response to arousal from sleep is reduced in children with DS compared with healthy children. Twenty children aged 3-17y referred for investigation of sleep disordered breathing (10 DS; 10 obstructive sleep apnea (OSA) controls) matched for age and obstructive apnea/hypopnea index (OAHI) underwent routine overnight polysomnography. In addition 10 non-snoring controls from the general community were studied. Beat-by-beat HR was analysed from 15s pre to 15s post spontaneous arousals and compared between groups using 2-way ANOVA with repeated measures. Data are presented as mean +/- SEM. For both NREM and REM, arousals were associated with a significant increase in HR in all groups (Peak response NREM: DS 118+/-1 % at 3s, OSA controls 124+/-2 % at 4s, Healthy controls 125+/-3 % at 4s. Peak response REM: DS 116+/-2 % at 4s, OSA controls 123+/-3 % at 4s, Healthy controls 125+/-4 at 4s, p<0.001 for all). Posthoc analysis revealed that HR in the DS group was significantly lower than the both control groups at 1-4 s in NREM, and at 4-5 s in REM (p<0.05 for all). In conclusion, the HR response to spontaneous arousal from sleep is reduced in children with DS compared with healthy children. This attenuated cardiovascular response could be due to reduced sympathetic activation or blunted vagal withdrawal and may have implications for the child with DS and OSA.
TÍTULO / TITLE:
- Prevalence of congenital heart defects and persistent pulmonary hypertension of the neonate with Down syndrome.
RESUMEN / SUMMARY:
-
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REVISTA / JOURNAL:
- Eur J Pediatr. 2010 Apr 23.
AUTORES / AUTHORS:
- Weijerman ME; van Furth AM; van der Mooren MD; van Weissenbruch MM; Rammeloo L; Broers CJ; Gemke RJ
INSTITUCIÓN / INSTITUTION:
- Department of Paediatrics, Subdivision of General Paediatrics and Infectious Diseases, VU University Medical Center, Amsterdam, the Netherlands
weijerman@vumc.nl
RESUMEN / SUMMARY:
- The aim of this study was to assess the prevalence of congenital heart defects (CHDs) and persistent pulmonary hypertension of the neonate (PPHN) in children with Down syndrome (DS) and to assess its impact on neonatal factors. It was a prospective study of a birth cohort of children with DS born between 2003 and 2006 registered by the Dutch Paediatric Surveillance Unit (DPSU). A CHD occurred in 43% of 482 children with trisomy 21. Atrioventricular septal defect was found in 54%, ventricular septal defect in 33.3% and patent ductus arteriosus in 5.8%. The incidence of PPHN in DS was 5.2%, which is significantly higher than the general population (p < 0.001). The reported mortality in newborns with DS was overall 3.3% and was still significant higher in children with a CHD versus no CHD (5.8% versus 1.5%) (p = 0.008). The presence of CHD in children with DS had no influence on their birth weight, mean gestational age and Apgar score. In neonates with DS, we found not only a 43% prevalence of CHD, but also a high incidence of PPHN at 5.2%. Early recognition of the cardiac condition of neonates with DS seems justified.
TÍTULO / TITLE:
- LYMPHATIC CAPILLARY HYPOPLASIA IN THE SKIN OF FETUSES WITH INCREASED NUCHAL TRANSLUCENCY AND TURNER`S SYNDROME: COMPARISON WITH TRISOMIES AND CONTROLS
RESUMEN / SUMMARY:
REVISTA / JOURNAL:
- MOLECULAR HUMAN REPRODUCTION, eFIRST date: 11 MAY 2010
AUTORES / AUTHORS:
- von Kaisenberg, CS; Wilting, J; Doerk, T; Nicolaides, KH; Meinhold-Heerlein, I; Hillemanns, P; Brand-Saberi, B
RESUMEN / SUMMARY:
- Fetuses with Turner syndrome or trisomies 21, 18 and 13 show excess of skin which can be visualized by ultrasonography as increased nuchal translucency at 11-13+6 weeks` gestation. The objective of this study was to gain insight in the development and distribution of blood vessels, lymphatic capillaries of the cutis and lymphatic collectors of the cutis and subcutis and to study developmental changes with increasing gestation. Immunofluorescence of cryo-sections with ten specific antibodies was used to investigate the nuchal skin of three fetuses with Turner syndrome and to differentiate lymphatics, lymph capillaries (FLT4, PTN 63, LYVE1, PROX1), blood vessels (KDR, CD 31, PDPN), blood clotting activity (von Willebrand Factor), basement membranes and big vessels (Laminin, Collagen Type IV). The findings were compared with those in seven fetuses with trisomy 21 and two fetuses each with trisomies 18 or 13, respectively, as well as six normal controls. Immunoreactive recept! ors for vascular endothelial growth factors (FLT4) were decreased in lymphatic capillaries of the skin of Turner fetuses. Accordingly, LYVE1 was scarce and PROX1 staining was less intense in the dermis of Turner fetuses. Lymphatic collectors were however evenly stained. In normal fetuses and in those with trisomies, lymphatic capillaries were evenly distributed. We conclude that lymphatic capillary hypoplasia might be responsible for nuchal cystic hygroma in Turner Syndrome. The biological basis for increased nuchal translucency in trisomies may however be different.
TÍTULO / TITLE:
- Mortality after total cavopulmonary connection in children with the down syndrome.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- Am J Cardiol. 2010 Mar 15;105(6):865-8.
AUTORES / AUTHORS:
- Gupta-Malhotra M; Larson VE; Rosengart RM; Guo H; Moller JH
INSTITUCIÓN / INSTITUTION:
- Division of Pediatric Cardiology, Children’s Memorial Hermann Hospital, University of Texas, Houston, Texas, USA.
monesha.gupta@uth.tmc.edu
RESUMEN / SUMMARY:
- A total cavopulmonary connection (Fontan surgery) is rarely performed in a child with trisomy 21 (Down syndrome) for a univentricular heart, and the outcomes after surgery are not well defined, but the incidence of mortality has been reported to be higher. To determine the mortality rate and contributing factors after Fontan surgery in children with Down syndrome, mortality data after Fontan surgery from the Pediatric Cardiac Care Consortium Registry were evaluated. Among Fontan procedures (n = 2,853), all patients with Down syndrome (n = 17) were selected, of whom 13 had hemodynamic data available. Thirteen children without chromosomal aberrations were then selected as a control group, matched 1 to 1 for gender, age, weight, lesion, and type of Fontan procedure. The following variables were evaluated: pulmonary artery pressure and vascular resistance, weight, hemoglobin, degree of atrioventricular regurgitation, previous Glenn operation, fenestration, and length of stay in the hospital. In children with Down syndrome, mortality after the Glenn operation was 28%. Mortality after the Fontan operation was increased significantly (p = 0.001) in children with Down syndrome (35%) compared with those without Down syndrome (10%). Between patients with Down syndrome and controls, there were no significant differences in the perioperative parameters evaluated. Almost all mortality was in the early postoperative period in children with Down syndrome. The relative risk ratio of mortality was 2.5 (95% confidence interval 0.63 to 10). In conclusion, Down syndrome was found to be an independent parameter associated with a significantly higher risk for mortality in the early postoperative period after Fontan surgery.
TÍTULO / TITLE:
- Meeting Oral Health Needs to Promote the Well-Being of the Geriatric Population: Educational Research Issues
RESUMEN / SUMMARY:
REVISTA / JOURNAL:
- JOURNAL OF DENTAL EDUCATION, 74 (1): 29-35 JAN 2010
AUTORES / AUTHORS:
- Ettinger, RL
RESUMEN / SUMMARY:
-
This article reviews some of the more recent demographic changes affecting aging populations. The author expands the concept of aging to include persons who may be chronologically young but biologically old because they are medically compromised or developmentally disabled. It is not known how many persons can be included in this definition who will need care, and the question is what are their needs and how are we going to teach dental students and dentists to care for them. These problems are discussed, and some models of care are described.
TÍTULO / TITLE:
- Periodontal health in Down syndrome: Contributions of mental disability, personal, and professional dental care.
RESUMEN / SUMMARY:
-
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REVISTA / JOURNAL:
- Spec Care Dentist. 2010 May;30(3):118-23.
AUTORES / AUTHORS:
- Khocht A; Janal M; Turner B
INSTITUCIÓN / INSTITUTION:
- Associate Professor, Temple University School of Dentistry, Philadelphia, Pennsylvania.
RESUMEN / SUMMARY:
- ABSTRACT Fifty-five dentate patients with Down syndrome (DS) and 74 with mental disability non-Down (MR) were compared to 88 control subjects. Subjects in the MR and Control groups were matched by gender and ethnicity to subjects with DS. All subjects were nonsmokers. Periodontal evaluation included plaque index (PI), gingival index (GI), bleeding on probing (BOP), and clinical periodontal attachment levels. Caries and missing teeth were recorded. Measures of personal dental hygiene and the frequency of professional dental care were also recorded. Most subjects brushed their teeth at least once per day, but did not floss. Both groups with DS and MR had significantly more missing teeth, more BOP, and higher GI and PI levels than the control group. Patients with DS had more attachment loss (AL) than the other two groups (p < .001). Increased AL in patients with DS was not associated with differences in socioeconomic status, personal/professional dental care, or mental disability.
TÍTULO / TITLE:
- Mothers’ perceptions concerning oral health of children and adolescents with Down syndrome: a qualitative approach.
RESUMEN / SUMMARY:
-
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REVISTA / JOURNAL:
- Eur J Paediatr Dent. 2010 Mar;11(1):27-30.
AUTORES / AUTHORS:
- Oliveira AC; Pordeus IA; Luz CL; Paiva SM
INSTITUCIÓN / INSTITUTION:
- Department of Social and Preventive Dentistry, Faculty of Dentistry, Federal University of Minas Gerais, Minas Gerais, Brazil.
RESUMEN / SUMMARY:
- AIM: The aim of this qualitative study was to investigate the perceptions of a group of mothers of children and adolescents with Down syndrome (DS) concerning the overall health and oral health of their children. METHODS: The information was collected interviewing in depth 19 mothers using an open-ended orientation form. To investigate the perceptions of the mothers was carried out a thematic content analysis. Two general themes were addressed: mothers’ perceptions concerning the health of the child with DS and mothers’ opinion on the impact of oral health on the life of the child with DS. RESULTS: According to the interviews, for the mothers, overall health and oral health entail specificities associated mainly with the absence of illness, the performance of daily activities, and feelings of well-being. Mothers tended to hold themselves accountable for their children’s health status. Within the situations these women experience, many of the interviewees reported difficulties in caring for their children’s oral health. CONCLUSION: Factors linked to financial constraints, time, and access to healthcare referral services hamper the search for specialised dental care for individuals with special needs.
TÍTULO / TITLE:
- Feeding and nonnutritive sucking habits and prevalence of open bite and crossbite in children/adolescents with Down syndrome.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- Angle Orthod. 2010 Jul;80(4):560-5.
AUTORES / AUTHORS:
- Oliveira AC; Pordeus IA; Torres CS; Martins MT; Paiva SM
INSTITUCIÓN / INSTITUTION:
- Department of Social and Preventive Dentistry, Federal University of Minas Gerais, Minas Gerais, Brazil.
anacboliveira@yahoo.com.br
RESUMEN / SUMMARY:
- OBJECTIVE: To analyze the influence of breastfeeding, bottle feeding, and nonnutritive sucking habits on the prevalence of open bite and anterior/posterior crossbite in children with Down syndrome (DS). MATERIALS AND METHODS: A cross-sectional study was carried out in 112 pairs of mothers/children with DS between 3 and 18 years of age at a maternal/children’s hospital in Rio de Janeiro, Brazil. The children with DS were clinically examined for the presence of open bite as well as anterior and posterior crossbite. Information on breastfeeding, bottle feeding, and nonnutritive sucking habits was collected using a structured questionnaire. The control variables were age and mouth posture of children/adolescents and mother’s schooling. Statistical analysis of the data was performed using the chi-square test and multiple logistic regression. RESULTS: The prevalence of anterior open bite was 21%, anterior crossbite was 33%, and posterior crossbite was 31%. The use of bottle feeding for more than 24 months (prevalence ratio [PR] = 1.6) was associated with the occurrence of open bite. Having breastfed for less than 6 months (PR = 1.4) and pacifier sucking for more than 24 months (PR = 3.1) were associated with the prevalence of anterior crossbite. Finger sucking (PR = 2.9) and the use of bottle feeding for more than 24 months (PR = 2.6) were associated with posterior crossbite. CONCLUSION: The prevalence of open bite and crossbite in children with DS was associated with the use of bottle feeding and pacifier sucking for more than 24 months, breastfeeding for less than 6 months, and finger sucking.
TÍTULO / TITLE:
- Patterns of tooth agenesis in patients with Down syndrome in relation to hypothyroidism and congenital heart disease: an aid for treatment planning.
RESUMEN / SUMMARY:
-
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REVISTA / JOURNAL:
- Am J Orthod Dentofacial Orthop. 2010 May;137(5):584-5.
AUTORES / AUTHORS:
- Reuland-Bosma W; Reuland MC; Bronkhorst E; Phoa KH
INSTITUCIÓN / INSTITUTION:
- Rotterdam, Amsterdam, and Nijmegen, The Netherlands.
wimke@reuland.nl
RESUMEN / SUMMARY:
- INTRODUCTION: The purposes of this study were to investigate the patterns of tooth agenesis (oligodontia and nonoligodontia), maxillary canine impaction, and tooth transposition in subjects with Down syndrome and to determine whether congenital heart disease and hypothyroidism are parameters in tooth agenesis. METHODS: The study included 114 patients with Down syndrome. The data were quantified by using standardized records, clinical examinations, panoramic radiographs, and solo roentgenograms. The subjects were differentiated into oligodontia (6 or more teeth missing) and nonoligodontia (5 or fewer teeth missing). RESULTS: In these patients with Down syndrome, 59.6% had missing teeth. Those in the nonoligodontia group showed a tendency toward a negative correlation between congenital heart disease and agenesis (P = 0.093; odds ratio = 0.49) but a slight positive correlation between hypothyroidism and agenesis (P = 0.060; odds ratio = 3.71). In the oligodontia group, there was a quantitatively and qualitatively different pattern, indicating another phenotype. When both mandibular central incisors were missing, there was a remarkable chance for oligodontia (P = 0.001; odds ratio = 38.8). In the mandible, symmetrical agenesis of the canines and lateral incisors was more frequent in the nonoligodontia group. CONCLUSIONS: The oligodontia (with a different phenotype) and nonoligodontia groups had different patterns of agenesis. Maxillary canine impaction was not related to absence of the lateral incisors. Absence of both mandibular central incisors was a high predictor for oligodontia. Congenital heart disease and hypothyroidism are parameters involved in tooth agenesis.
TÍTULO / TITLE:
- Orthodontics and foetal pathology: a personal view on craniofacial patterning
RESUMEN / SUMMARY:
REVISTA / JOURNAL:
- EUROPEAN JOURNAL OF ORTHODONTICS, 32 (2): 140-147 APR 2010
AUTORES / AUTHORS:
- Kjaer, I
RESUMEN / SUMMARY:
- The fields described cover all areas seen on profile, frontal, and panoramic radiographs. The fields are the theca, frontonasal, maxillary, palatine, and mandibular together with the cerebellar field and cervical spine. Regional fields in the dentition are described according to the pattern of peripheral nerve innervation. Studies on severely malformed foetuses show that the malformation can occur solely within a single field or in several fields. This is the background for these personal views on craniofacial patterning. These new views may assist in the diagnosis and interpretation of malformations in the cranium and dentition.
TÍTULO / TITLE:
- Effects of oral care in Down syndrome children with obstructive sleep apnea.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- J Oral Sci. 2010;52(1):145-7.
AUTORES / AUTHORS:
- Sato K; Shirakawa T; Niikuni N; Sakata H; Asanuma S
INSTITUCIÓN / INSTITUTION:
- Department of Pediatric Dentistry, Nihon University School of Dentistry, Tokyo, Japan
onodera-k@dent.nihon-u.ac.jp
RESUMEN / SUMMARY:
- Down syndrome (DS) children with sleep apnea often present with oral breathing associated with nasal obstruction. This causes the oral cavity and pharynx to become dry. We describe the treatment of three DS children with sleep apnea who were treated using products for oral dryness. Snoring disappeared after treatment in two of the children and apnea disappeared in all three. The symptoms of a reddened oral mucosa and coated tongue disappeared in all three DS children. Saliva pH testing demonstrated that the pH value increased in all of the children after treatment. These results indicate that oral care can improve the oral hygiene status of DS children, and that proper oral care can help prevent oral mucosal dryness and thereby reduce sleep apnea symptoms.
TÍTULO / TITLE:
- Oral disease in children with Down syndrome: causes and prevention.
RESUMEN / SUMMARY:
-
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REVISTA / JOURNAL:
- Community Pract. 2010 Feb;83(2):18-21.
AUTORES / AUTHORS:
- Shore S; Lightfoot T; Ansell P
INSTITUCIÓN / INSTITUTION:
- Hull York Medical School, York.
RESUMEN / SUMMARY:
- While healthcare professionals may be familiar with the social and medical management of Down syndrome, dental issues have traditionally been somewhat neglected and are important causes of morbidity. The aims of this review are two-fold. Firstly, to draw attention to the environmental and host factors associated with periodontal disease and dental caries (tooth decay) in children with Down syndrome. Secondly, to highlight key yet largely modifiable risk factors in the causation and progression of these chronic oral conditions, many of which also apply to other children with learning disabilities. The review focuses on the role of community and school-based healthcare professionals in promoting good oral health using evidence-based preventative strategies, and in encouraging early, regular contact with dental services.
TÍTULO / TITLE:
- The masticatory normative indicator.
RESUMEN / SUMMARY:
-
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REVISTA / JOURNAL:
- J Dent Res. 2010 Mar;89(3):281-5. Epub 2010 Jan 29.
AUTORES / AUTHORS:
- Woda A; Nicolas E; Mishellany-Dutour A; Hennequin M; Mazille MN; Veyrune JL; Peyron MA
INSTITUCIÓN / INSTITUTION:
- Universite Clermont 1, EA 3847, Faculty of Dentistry, 11 bd Charles-de-Gaulle, 63000 Clermont-Ferrand, France.
Alain.WODA@u-clermont1.fr
RESUMEN / SUMMARY:
- There is no established quantitative, objective method to differentiate individuals with good masticatory function from those lacking this attribute. The aim of this study was to specify a normal range of median particle size values for masticated raw carrots collected just before being swallowed. The masticatory normative indicator (MNI) value thus obtained was based on seven studies carried out by different investigators using different methods for measuring particle size in carrot boluses. A simple mathematical transformation of variables and the choice of an interval of +/-1.96 times the standard deviation gave 4.0 mm as the upper limit of normal median particle size for carrots in a population of young persons with good oral health. This value identifies boluses that may be considered as resulting from impaired mastication, as illustrated in healthy individuals with experimentally hampered mastication, denture wearers, and individuals presenting with obesity or Down syndrome.
TÍTULO / TITLE:
- Eruptive syringoma in a patient with trisomy 21.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- Singapore Med J. 2010 Feb;51(2):e46-7.
AUTORES / AUTHORS:
- Ong GC; Lim KS; Chian LY
INSTITUCIÓN / INSTITUTION:
- Department of Dermatology, National Skin Centre, Singapore.
gavinong@nsc.gov.sg
RESUMEN / SUMMARY:
- Syringomas are benign adnexal neoplasia that are classified into four main types, according to their clinical features and associations. Syringoma associated with trisomy 21 typically presents with a periorbital cutaneous involvement. We report an 18-year-old Chinese girl with trisomy 21, who presented with eruptive syringoma, an unusual generalised form involving her trunk and limbs. A histological examination was performed to confirm the diagnosis.
TÍTULO / TITLE:
- Prevalence of Acne Vulgaris in Patients with Down Syndrome.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- Dermatology. 2010 Mar 23.
AUTORES / AUTHORS:
- Bagatin E; Kamamoto CS; Dos Santos Guadanhim LR; Sanudo A; Costa Dias M; Barraviera IM; Consolim Colombo F
INSTITUCIÓN / INSTITUTION:
- Universidade Federal de Sao Paulo, Sao Paulo, Brasil.
RESUMEN / SUMMARY:
- Background/Objective: Acne vulgaris exhibits a worldwide prevalence of up to 95% among adolescents. On the other hand, Down syndrome is an autosomal chromosomal disorder with associated dermatoses and a tendency to obesity. There are no data on its association with acne. Our aim was to detect the prevalence of acne, its forms and associated factors in Down syndrome. Method: A cross-sectional study including 89 subjects aged 10-28 years from Associacao de Pais e Amigos dos Excepcionais-Sao Paulo to verify acne, metabolic and hormonal disorders by interview, clinical and laboratory examinations. Results: We evaluated 49 (55%) males and 40 (45%) females. A weak agreement between self-estimation for acne and examination result was detected. The overall prevalence of acne was 70.8%: 83.7% in males and 55% in females. The prevalence of acne in the age groups 10-17 and 18-28 was 62 and 78.7%, respectively. Facial comedonal acne was mostly detected. The prevalence of obesity was 40%, that of metabolic disorders 7% and that of hyperandrogenism (in females) 15%. Except for gender, no other factor evaluated correlated with acne. Conclusion: A low prevalence of acne in Down syndrome, a predominance in males aged 18-28 and a facial comedonal form were detected. An association with obesity, metabolic disorders or hyperandrogenemia was not assessed.
EAR/NASAL - OTORRINOLARINGOLOGÍA
TÍTULO / TITLE:
- Quantification of vocal tract configuration of older children with Down syndrome: a pilot study.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- Int J Pediatr Otorhinolaryngol. 2010 Apr;74(4):378-83. Epub 2010 Feb 11.
AUTORES / AUTHORS:
- Xue SA; Kaine L; Ng ML
INSTITUCIÓN / INSTITUTION:
- Division of Speech and Hearing Sciences, The University of Hong Kong, Pokfulam, Hong Kong.
axue@hkucc.hku.hk
RESUMEN / SUMMARY:
- OBJECTIVE: To quantify the vocal tract (VT) lumen of older children with Down syndrome using acoustic reflection (AR) technology. DESIGN: Comparative study. SETTING: Vocal tract lab with sound-proof booth. PARTICIPANTS: Ten children (4 males and 6 females), aged 9-17 years old diagnosed with Down syndrome. Ten typically developing children (4 males and 6 females) matched for age, gender, and race. INTERVENTION: Each participant’s vocal tract measurements were obtained by using an Eccovision Acoustic Pharyngometer. MAIN OUTCOME MEASURES: Six vocal tract dimensional parameters (oral length, oral volume, pharyngeal length, pharyngeal volume, total vocal tract length, and total vocal tract volume) from children with Down syndrome and the typically developing children were measured and compared. RESULTS: Children with Down syndrome exhibited small oral cavities when compared to control group (F(1,18)=6.55, p=0.02). They also demonstrated a smaller vocal tract volumes (F(1,18)=2.58, p=0.13), although the results were not statistically significant at the 0.05 level. Pharyngeal length, pharyngeal volume, and vocal tract length were not significantly different between the two groups. CONCLUSION: Children with Down syndrome had smaller oral cavities, and smaller vocal tract volumes. No significant differences were found for pharyngeal length, pharyngeal volume, and vocal tract length between these two groups.
ENDOCRINOLOGY/NUTRITION - ENDOCRINOLOGÍA/NUTRICIÓN
TÍTULO / TITLE:
- Down`s syndrome in diabetic patients aged < 20 years: an analysis of metabolic status, glycaemic control and autoimmunity in comparison with type 1 diabetes
RESUMEN / SUMMARY:
REVISTA / JOURNAL:
- DIABETOLOGIA, 53 (6): 1070-1075 JUN 2010
AUTORES / AUTHORS:
- Rohrer, TR; Hennes, P; Thon, A; Dost, A; Grabert, M; Rami, B; Wiegand, S; Holl, RW
RESUMEN / SUMMARY:
- Intellectual impairment in individuals with Down`s syndrome and diabetes mellitus potentially limits the quality of diabetic control. In addition, these patients are at risk of having immunological abnormalities. The present study compared metabolic status and concomitant diseases in young (< 20 years old) Down`s syndrome patients with diabetes vs young type 1 diabetic patients.
The Diabetes-Patienten-Verlaufsdaten is a longitudinal follow-up database, which collects data from 298 German and Austrian diabetes centres. Data available on diabetic patients aged < 20 years were analysed statistically.
We compared data for 159 Down`s syndrome patients with diabetes and 41,983 type 1 diabetic patients. The former used less insulin, but showed better glycaemic control (HbA(1c)). Diabetes onset during the first 3 years of life occurred in 18.9% of Down`s syndrome patients with diabetes and in 6.4% of type 1 diabetic patients. Antibody titres indicative of coeliac disease and thyroid peroxidase antibodies were more frequent in Down`s syndrome patients with diabetes. No significant differences were found regarding the beta cell autoantibodies studied.
The age-of-onset distribution showed a shift towards younger ages and was bimodal in the Down`s syndrome group. The better metabolic control found, despite intellectual impairment, in young Down`s syndrome patients with diabetes cannot be conclusively explained by our data, but is likely to be due to a less complex lifestyle. Our data provide further confirmation that coeliac and thyroid antibodies are more prevalent in Down`s syndrome. The presence of beta cell autoantibodies supports an autoimmune cause of diabetes in some children with Down`s syndrome.
TÍTULO / TITLE:
- Deficiencia de vitamina A y estado nutricional en pacientes con Sindrome de Down. Vitamin A deficiency and nutritional status in patients with Down’s syndrome.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- An Pediatr (Barc). 2010 Mar;72(3):185-90. Epub 2010 Feb 11.
AUTORES / AUTHORS:
- Chavez CJ; Ortega P; Leal J; D’Escrivan A; Gonzalez R; Miranda LE
INSTITUCIÓN / INSTITUTION:
- Instituto de Investigaciones Biologicas, Universidad del Zulia, Maracaibo, Venezuela.
biomolecula@hotmail.com
RESUMEN / SUMMARY:
- INTRODUCTION: Vitamin A deficiency (VAD) is a worldwide public health problem. Epidemiological studies of VAD prevalence have been conducted in individuals with chromosome load and genetic potential compared with the general population; however, there are few studies in patients with Down’s syndrome (DS). The objective of this study was to determine the prevalence of VAD and analyse nutritional status in patients with DS. METHODS: A prospective and cross-sectional study was performed, with 50 karyotypically normal (KN) individuals (10.4+/-3.7 years old) and 38 randomly selected patients with DS (8.2+/-4.1 years old). Serum retinol was determined by HPLC using the Bieri method, with an international reference standard to define VAD (serum retinol <20 microg/dL). The data were analysed using the SAS/STAT statistical program. RESULTS: The prevalence of VAD was 18.4% in individuals with DS and 4% in KN individuals (OR: 5.42; 95% CI=0.93-40.64; p=0.02). Children with DS between two and six years old shown a significativily lower serum retinol (p=<0.05).The patients with DS also showed a significant decrease in height and weight compared to KN (p=<0.001). CONCLUSIONS: The prevalence of VAD detected in patients with DS could be considered a public health problem. Also, the chromosome 21 trisomy represent a risk factor associated with VAD.
TÍTULO / TITLE:
- Down’s syndrome in diabetic patients aged <20 years: an analysis of metabolic status, glycaemic control and autoimmunity in comparison with type 1 diabetes.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- Diabetologia. 2010 Feb 26.
AUTORES / AUTHORS:
- Rohrer TR; Hennes P; Thon A; Dost A; Grabert M; Rami B; Wiegand S; Holl RW
INSTITUCIÓN / INSTITUTION:
- Department of Paediatrics and Neonatology, Saarland University Hospital, Kirrberger Str. 1, Geb. 9, 66421, Homburg/Saar, Germany
tilman.rohrer@uniklinikum-saarland.de
RESUMEN / SUMMARY:
- AIMS/HYPOTHESIS: Intellectual impairment in individuals with Down’s syndrome and diabetes mellitus potentially limits the quality of diabetic control. In addition, these patients are at risk of having immunological abnormalities. The present study compared metabolic status and concomitant diseases in young (<20 years old) Down’s syndrome patients with diabetes vs young type 1 diabetic patients. METHODS: The Diabetes-Patienten-Verlaufsdaten is a longitudinal follow-up database, which collects data from 298 German and Austrian diabetes centres. Data available on diabetic patients aged <20 years were analysed statistically. RESULTS: We compared data for 159 Down’s syndrome patients with diabetes and 41,983 type 1 diabetic patients. The former used less insulin, but showed better glycaemic control (HbA(1c)). Diabetes onset during the first 3 years of life occurred in 18.9% of Down’s syndrome patients with diabetes and in 6.4% of type 1 diabetic patients. Antibody titres indicative of coeliac disease and thyroid peroxidase antibodies were more frequent in Down’s syndrome patients with diabetes. No significant differences were found regarding the beta cell autoantibodies studied. CONCLUSIONS/INTERPRETATION: The age-of-onset distribution showed a shift towards younger ages and was bimodal in the Down’s syndrome group. The better metabolic control found, despite intellectual impairment, in young Down’s syndrome patients with diabetes cannot be conclusively explained by our data, but is likely to be due to a less complex lifestyle. Our data provide further confirmation that coeliac and thyroid antibodies are more prevalent in Down’s syndrome. The presence of beta cell autoantibodies supports an autoimmune cause of diabetes in some children with Down’s syndrome.
TÍTULO / TITLE:
- Cytogenetic and epidemiological profiles of Down syndrome in a Moroccan population: a report of 852 cases.
RESUMEN / SUMMARY:
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REVISTA / JOURNAL:
- Singapore Med J. 2010 Feb;51(2):133-6.
AUTORES / AUTHORS:
- Jaouad IC; Cherkaoui Deqaqi S; Sbiti A; Natiq A; Elkerch F; Sefiani A
INSTITUCIÓN / INSTITUTION:
- Department of Medical Genetics, National Institute of Health, Rabat, Morocco.
imane_cj@yahoo.fr
RESUMEN / SUMMARY:
- INTRODUCTION: Trisomy 21 or Down syndrome is the most common type of autosomal chromosome abnormality, with an incidence of one out of 700 live births. Down syndrome is associated with psychomotor delay, characteristic facial features, and sometimes, cardiac, digestive and ocular malformations. The aim of this study was to estimate the proportions of various cytogenetic types of trisomy 21, and to study the link between maternal age and trisomy 21 in the Moroccan population, in order to provide data on the cytogeneticity and epidemiology of Down syndrome in Morocco. METHODS: A retrospective analysis was performed on the case records of 852 patients who were confirmed as Down syndrome by cytogenetic analysis at the Department of Medical Genetics, National Institute of Health, Morocco. RESULTS: Among the 852 cases of Down syndrome presenting over a period of 15 years, free trisomy 21 was present in 820 cases (96.24 percent). 27 patients had translocation and five cases were mosaics. The median maternal age of the Moroccan mothers at the birth of the affected child was 35.39 years. CONCLUSION: The identification of specific types of chromosomal abnormalities in Down syndrome children is important as it assists with patient management and family counselling.
TÍTULO / TITLE:
- Survival of children with mosaic Down syndrome.
RESUMEN / SUMMARY:
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REVISTA / JOURNAL:
- Am J Med Genet A. 2010 Mar;152ª(3):800-1.
AUTORES / AUTHORS:
- Shin M; Siffel C; Correa A
INSTITUCIÓN / INSTITUTION:
- National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA
mshin@cdc.gov
RESUMEN / SUMMARY:
-
TÍTULO / TITLE:
- Prevalence of Down’s syndrome in a pregnant population in Finland.
RESUMEN / SUMMARY:
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REVISTA / JOURNAL:
- - Acta Obstet Gynecol Scand. 2010 Mar 11.
AUTORES / AUTHORS:
- Marttala J; Yliniemi O; Gissler M; Nieminen P; Ryynanen M
INSTITUCIÓN / INSTITUTION:
- Department of Obstetrics and Gynecology.
RESUMEN / SUMMARY:
- Abstract The characteristics of the Finnish parturient have changed in recent years. The mean age of mothers at first delivery is now 29.3 years and the number of women > 35 years of age has increased to 19%. This shift has led to an increase in the prevalence of Down’s syndrome. Between 1 January 2002 and 31 December 2006, there were 795 cases of Down’s syndrome (27/10,000) in the Finnish Register of Congenital Malformations. The distribution of Down’s syndrome in terminated pregnancies and newborns was analyzed in 5-year periods based on maternal age. The distribution of Down’s syndrome cases in younger women (< 35 years) and in older women (>/=35 years) at the time of delivery was compared. The majority of new Down’s syndrome cases occurred in the group having older women (61.1%), even though 35 years is the arbitrary threshold.
GASTROENTEROLOGY - GASTROENTEROLOGÍA
TÍTULO / TITLE:
- When to Screen Children with Down Syndrome for Celiac Disease?
RESUMEN / SUMMARY:
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REVISTA / JOURNAL:
- J Trop Pediatr. 2010 Apr 13.
AUTORES / AUTHORS:
- Pavlovic M; Radlovic N; Lekovic Z; Stojsic Z; Puleva K; Berenji K
INSTITUCIÓN / INSTITUTION:
- Department of Pediatrics, General Hospital Subotica, Izvorska 3, 24000 Subotica, Serbia.
RESUMEN / SUMMARY:
- The coexistence of Down syndrome (DS) and celiac disease (CD) has been reported in many studies. In our study, we examined 82 children with DS aged 8 months to 8.6 years for the existence of CD using serological markers immunoglobulin A (IgA) and immunoglobulin G (IgG) transglutaminase antibodies, followed by follow-up determination of total IgA levels. In four children who were positive for one of the above-mentioned antibodies, enteric biopsy has been performed that showed absence of CD. Our findings raise doubt about the need for obligatory serological screening of children with DS aged <8 years.
TÍTULO / TITLE:
- Recurrent pancreatitis caused by pancreatobiliary anomalies in children with annular pancreas
RESUMEN / SUMMARY:
REVISTA / JOURNAL:
- JOURNAL OF PEDIATRIC SURGERY, 45 (4): 741-746 APR 2010
AUTORES / AUTHORS:
- Urushihara, N; Fukumoto, K; Fukuzawa, H; Suzuki, K; Matsuoka, T; Kawashima, S; Watanabe, K; Hasegawa, S
RESUMEN / SUMMARY:
- Purpose: Annular pancreas (AP) is usually associated with duodenal obstruction in neonates. Pancreatitis with AP occurs frequently in adults but is rare in children. This article describes pancreatitis in children with AP and pancreatobiliary anomalies and its surgical treatment.
Patients and Methods: Six children who underwent duodenal bypass for AP subsequently developed recurrent pancreatitis. Three had trisomy 21. Duodenoduodenostomy had been performed in 5 patients and gastrojejunostomy in 1 patient for neonatal duodenal obstruction. We reviewed overall management, imaging, and surgical treatment in these children.
Results: All children subsequently complained of recurrent abdominal pain. Pancreatitis developed in 6 children, and magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography (ERCP) revealed associated pancreatobiliary anomalies such as pancreas divisum, pancreatobiliary malunion, choledochocele, and intraluminal duodenal diverticulum. In 5 cases, surgery for recurrent or chronic pancreatitis was performed. The range of follow-up was 11 to 54 months, and all children who underwent surgery had excellent results.
Conclusions: Children with AP occasionally require reoperation for recurrent pancreatitis because of associate pancreatobiliary anomalies. Magnetic resonance cholangiopancreatography and ERCP provide excellent images of pancreatobiliary anomalies. Intraoperative cholangiopancreatography is also essential for accurate depiction of the ductal structure and selection of the appropriate surgical procedure. (C) 2010 Elsevier Inc. All rights reserved.
TÍTULO / TITLE:
- Coeliac disease as the cause of resistant sideropenic anaemia in children with Down’s syndrome: case report.
RESUMEN / SUMMARY:
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REVISTA / JOURNAL:
- Srp Arh Celok Lek. 2010 Jan-Feb;138(1-2):91-4.
AUTORES / AUTHORS:
- Pavlovic M; Radlovic N; Lekovic Z; Berenji K; Stojsic Z; Radlovic V
INSTITUCIÓN / INSTITUTION:
- Paediatric Department, General Hospital, Subotica, Serbia.
momodec@tippnet.rs
RESUMEN / SUMMARY:
- INTRODUCTION: Coeliac disease (CD) is a permanent intolerance of gluten, i.e., of gliadin and related proteins found in the endosperm of wheat, rye and barley. It is characterized by polygenic predisposition, autoimmune nature, predominantly asymptomatic or atypical clinical course, as well as by high prevalence in patients with Down’s syndrome (DS) and some other diseases. OUTLINE OF CASES: We are presenting a girl and two boys, aged 6-7 (x = 6.33) years with DS and CD recognized under the feature of sideropenic anaemia resistant to oral therapy with iron. Beside mental retardation, low stature and the morphological features characteristic of DS, two patients had a congenital heart disease; one ventricular septal defect and the other atrioventricular canal. In two patients, trisomy on the 21st chromosome pair (trisomy 21) was disclosed in all cells, while one had a mosaic karyotype. All three patients had classical laboratory parameters of sideropenic anaemia: blood Hb 77-89 g/l (x = 81.67), HCT 0.26-0.29% (x = 0.28), MCV 69-80 fl (x = 73), MCH 24.3-30 pg (x = 26.77) and serum iron 2-5 micromol/L (x = 4.0). Beside anaemia and in one patient a mild isolated hypertransaminasemia (AST 67 U/l, ALT 62 U/l), other indicators of CD were not registered in any of the children. In addition, in all three patients, we also detected an increased level of antibodies to tissue transglutaminase (atTG) of IgA class (45-88 U/I) so that we performed endoscopic enterobiopsy in order to reliably confirm the diagnosis of CD. In all three patients, the pathohistological finding of the duodenal mucosa specimen showed mild to moderate destructive enteropathy associated with high intraepithelial lymphocyte infiltration, cryptic hyperplasia and lympho-plasmocytic infiltration of the stroma. In all three patients, the treatment with a strict gluten-free diet and iron therapy applied orally for 3-4 months resulted in blood count normalization and the correction of sideropenia. Serum level of the atTG-IgA, repeated after a 12-month diet, was also normal. CONCLUSION: CD should be taken into consideration in all cases of sideropenic anaemia resistant to iron oral therapy in children with DS. The diagnosis of CD implicates corresponding pathohistological confirmation, while the treatment of sideropenic anaemia and its complications, beside iron preparations, also requires compliance with a gluten-free diet.
TÍTULO / TITLE:
- Intestinal barrier gene variants may not explain the increased levels of antigliadin antibodies, suggesting other mechanisms than altered permeability
RESUMEN / SUMMARY:
REVISTA / JOURNAL:
- HUMAN IMMUNOLOGY, 71 (4): 392-396 APR 2010
AUTORES / AUTHORS:
- Wolters, VM; Alizadeh, BZ; Weijerman, ME; Zhernakova, A; van Hoogstraten, IMW; Mearin, ML; Wapenaar, MC; Wijmenga, C; Schreurs, MWJ
RESUMEN / SUMMARY:
- Various genes may influence intestinal barrier function, including MAGI2, MY09B, and PARD3, which are associated with celiac disease. Because direct measurement of intestinal permeability is difficult, antibodies against gliadin (AGA) and Baker`s yeast (anti-Saccharomyces cerevisiae antibodies [ASCA]) can be used as an indirect test. The objective of this study was to investigate whether intestinal permeability, represented by AGA, was correlated with MAGI2, MY09B, and PARD3. Analyses were performed in patients with Down syndrome, a population with suspected increased intestinal permeability. Correlations between AGA and ASCA were investigated. Patients with Down syndrome (n = 126) were genotyped for six single-nucleotide polymorphisms in MAGI2 (rs1496770, rs6962966, rs9640699), MY09B (rs1457092, rs2305764), and PARD3 (rs10763976). An allele dosage association of these risk genes and AGA levels was performed. The correlation between AGA and ASCA was studied. A strong corr! elation was found between AGA and ASCA (p < 0.01). The patient group with one or more risk genotypes had lower mean AGA levels (trend test p = 0.007) and consisted of a larger number of patients with normal AGA levels (p = 9.3 x 10(-5)). Celiac-associated risk genotypes are associated with lower AGA values instead of elevated ones. Thus, other immunologic phenomena play a role in the increased prevalence of elevated AGA in patients with Down syndrome, possibly involving altered induction and/or maintenance of tolerance.
TÍTULO / TITLE:
- Hepatic failure, neonatal hemochromatosis and porto-pulmonary hypertension in a newborn with trisomy 21 - a case report.
RESUMEN / SUMMARY:
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REVISTA / JOURNAL:
- Ital J Pediatr. 2010 May 18;36(1):38.
AUTORES / AUTHORS:
- Neil E; Cortez J; Joshi A; Bawle EV; Poulik J; Zilberman M; El-Baba MF; Sood BG
RESUMEN / SUMMARY:
- ABSTRACT: Liver failure in neonates is a rare but often fatal disease. Trisomy 21 is not usually associated with significant infantile liver disease. If present, hepatic dysfunction in an infant with Trisomy 21 is likely to be attributed to transient myeloproliferative disorder with hepatic infiltration by hematopoietic elements and may be associated with secondary hemosiderosis. A less commonly recognized cause of liver failure in neonates with Trisomy 21 is neonatal hemochromatosis (NH); this association has been reported in nine cases of Trisomy 21 in literature. NH is a rare, severe liver disease of intra-uterine onset that is characterized by neonatal liver failure and hepatic and extrahepatic iron accumulation that spares the reticuloendothelial system. NH is the most frequently recognized cause of liver failure in neonates and the commonest indication for neonatal liver transplantation. Although porto-pulmonary hypertension (PPH) has been reported as a complication of liver failure in adults and older children, this has not been reported in neonates with liver failure of any etiology. This is probably due to the rarity of liver failure in newborns, delayed diagnosis and high mortality. The importance of recognizing PPH is that it is reversible with liver transplantation but at the same time increases the risk of post-operative mortality. Therefore, early diagnosis of PPH is critical so that early intervention can improve the chances of successful liver transplantation. We report for the first time the association of liver failure with porto-pulmonary hypertension secondary to NH in an infant with Trisomy 21.
TÍTULO / TITLE:
- Clinical, cytogenetic, and molecular characterization of a girl with some clinical features of Down syndrome resulting from a pure partial trisomy 21q22.11-qter due to a de novo intrachromosomal dupli
RESUMEN / SUMMARY:
-
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REVISTA / JOURNAL:
- Genet Test Mol Biomarkers. 2010 Feb;14(1):57-65.
AUTORES / AUTHORS:
- Vaglio A; Milunsky A; Quadrelli A; Huang XL; Maher T; Mechoso B; Martinez S; Pagano S; Bellini S; Costabel M; Quadrelli R
INSTITUCIÓN / INSTITUTION:
- Institute of Medical Genetics, Hospital Italiano, Montevideo, Uruguay.
rquadr@dedicado.net.uy
RESUMEN / SUMMARY:
- We report a girl with a de novo pure partial trisomy 21 with some clinical features of Down syndrome. The girl patient presented a flat broad face, brachycephaly, and a flat nasal bridge. She also had upwardly slanted palpebral fissures, epicanthal folds, blepharitis, brushfield spots, and strabismus. Her mouth was wide with downturned corners, prominent lower lip, narrow and furrowed tongue, and short palate. G-banded chromosomal analysis of metaphases in cells from both skin and blood showed a 46,XX karyotype with additional chromosomal material on the distal short arm of one chromosome 21. Parental chromosomes were normal. Molecular analyses with the short-tandem-repeat (STR) marker D21S2039 (interferon-alpha/beta receptor [IFNAR]) (21q22.1) showed a triallelic pattern. Subtelomeric fluorescent in situ hybridization (FISH) analyses, LSI 13 (retinoblastoma 1 [RB1])/LSI 21(21q22.13-q22.2), and whole chromosome painting probes specific for chromosome 21 showed trisomy for the segment 21q22.13-21q22.2 due to a de novo intrachromosomal duplication. A 500K SNP microarray analysis was then performed and revealed a 13-Mb duplication of 21q22.11-qter. This duplicated material had been translocated onto the end of the “p” arm of one of the chromosome 21s. The karyotype was provisionally defined as 46,XX,add(21)(p12).ish der (21)t(21;21)(p12;q22.11)(WCP21q+,PCP21q++,D215259/D21S341/D21S342++)dn. At the age of 4 years and 10 months, a comprehensive psychological examination was performed and the diagnostic criteria for mental retardation were not fulfilled. In comparison with previously published cases of pure partial trisomy 21, this is a rare finding. Additional studies of such rare patients should aid in the study of the pathogenesis of Down syndrome.
TÍTULO / TITLE:
- Co-occurrence of achondroplasia and Down syndrome: Genotype/phenotype association.
RESUMEN / SUMMARY:
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REVISTA / JOURNAL:
- Birth Defects Res A Clin Mol Teratol. 2010 Mar 10.
AUTORES / AUTHORS:
- de Azevedo Moreira LM; Matos MA; Schiper PP; Carvalho AF; Gomes IC; Rolemberg JC; de Lima RL; Toralles MB
INSTITUCIÓN / INSTITUTION:
- Laboratory of Human Genetics and Mutagenesis, Biology Institute, Federal University of Bahia, Salvador, Bahia, Brazil.
RESUMEN / SUMMARY:
- BACKGROUND: This report describes the sixth case of an unusual association: Down syndrome with achondroplasia. It also analyzes the effects of both of these disorders on patient phenotype. METHODS: A male infant was evaluated for Down syndrome. His appearance also suggested a diagnosis of achondroplasia. The child was evaluated by physical examination, radiography, cytogenetic study, and mutation analysis. RESULTS: Chromosome analysis showed a karyotype of 47,XY,+21 in all 30 cells analyzed. Radiographic examination showed typical findings of achondroplasia, such as disproportionately large skull, shortening oflimb segments, and lumbar lordosis. FGFR3 screening showed a heterozygous G1138A mutation. CONCLUSIONS: The interaction of these two distinct genetic disorders in the same patient produces a phenotype typical of each syndrome with some overlapping signs. This case represents de novo origin of two disorders that both may be parental-age related.
TÍTULO / TITLE:
- Germ-line transmission of trisomy 21: Data from 80 families suggest an implication of grandmaternal age and a high frequency of female-specific trisomy rescue.
RESUMEN / SUMMARY:
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REVISTA / JOURNAL:
- Mol Cytogenet. 2010 Mar 18;3(1):7.
AUTORES / AUTHORS:
- Kovaleva NV
RESUMEN / SUMMARY:
- ABSTRACT: BACKGROUND: Trisomy of chromosome 21 (T21; Down syndrome, DS) is the most common aneuploidy in live births. Though its etiology has been intensively studied for a half of century, there are surprisingly many problems awaiting their elucidation. Some of the open questions are related directly to germ line mosaicism for T21, other problems include the prevalence of males with non-mosaic trisomy over females (skewed sex ratio, SR), the genetic predisposition to non-disjunction, etc. Studies in families of gonadal mosaicism (GM) carriers might help resolving some of these problems. RESULTS: 80 families of carriers of GM, in which the sex of the offspring had been specified, were identified in the literature and in logbooks of two local genetic units. Mothers in these families were relatively young: only 8 % of mothers were 35 years old and older at the time of delivery of their first affected offspring while the proportion of grandmothers on the GM carriers side aged 35 years old and older was significantly higher (39 %). Postzygotic rescue of T21 due to error in the meiosis I had been proposed as a mechanism of parental GM formation in 78% of the families with known origin of the T21. For the other 22%, rescue of errors in the meiosis II or postzygotic mitotic non-disjunction was assumed. Mosaicism for T21 in successive generations was reported in at least 12 families. The proportion of mosaics among affected female offspring (14%) is significantly higher compared to that among affected male offspring (0%). Male preponderance (SR = 1.5) is found in non mosaic liveborn offspring with either maternally- or paternally transmitted T21. Among unaffected offspring of male carriers of GM there is a notable excess of females (SR = 0.27). CONCLUSION: Both direct (results of cytogenetic and molecular study of the origin of trisomic line) and indirect (advanced grandmaternal age on the side of GM carrier) evidences allow to assume that significant proportion of the mosaic parents had been conceived as trisomics. Female-specific trisomy rescue and genetic predisposition to postzygotic non-disjunction have been suggested as mechanisms of formation of both GM and somatic mosaicism. Typical male preponderance in affected non mosaic offspring with either maternally- or paternally transmitted trisomy 21, indicates than meiotic events are not responsible for the skewed sex ratio in DS. However a female excess among unaffected offspring of male carriers of GM might be the result of meiotic non homologous co-orientation of chromosomes 21 and X in spermatogenesis.
TÍTULO / TITLE:
- ATYPICAL DOWN SYNDROME PHENOTYPE IN A GIRL WITH 21;21 TRANSLOCATION TRISOMY
RESUMEN / SUMMARY:
REVISTA / JOURNAL:
- GENETIC COUNSELING, 21 (1): 61-67 2010
AUTORES / AUTHORS:
-
INSTITUCIÓN / INSTITUTION:
- Tuysuz, B; Yavuz, A; Ozdil, M; Caferler, J; Ozon, H
RESUMEN / SUMMARY:
- Atypical Down syndrome phenotype in a girl with 21;21 translocation trisomy: We describe a girl with microcephaly, short stature, coarse face, severe growth and developmental delay, seizures, hypertonia, bilateral flexion contractures of the knees, and a de novo 2121 translocation trisomy 21 in peripheral blood lymphocytes. Fluorescence in situ hybridization (FISH) analysis confirmed the trisomy 21 translocation using whole chromosome painting probe 21 (WCP21). Chromosome analysis which was also performed on skin fibroblasts and revealed mosaicism for a translocation trisomy 21 cell line (22.3%) as well as a second cell line consisting of one normal chromosome 21 and a small ring chromosome 21 derived from the translocation 21q21q (61%) and a third line consisting of monosomy 21 (16.7%). FISH analyses by LSI21 probe for the critical (21q22.2-22.3) region of Down syndrome (DS) on interphase blood cells resulted with 30% two signals and 70% three signals, skin fibroblasts s! howed 84% single signal, 9% two signals and 7% three signals. The size airing chromosome 21 in skin fibroblasts was very small and probably there was a large, more proximally located deletion including chromosome 21q22 band. We consider that the atypical DS phenotype of the patient originated from the small ring chromosome 21 and the monosomy 21 in the skin fibroblasts and other tissues not available for analysis. Therefore, the clinical findings of the patient were most similar to monosomy 21 mosaicism syndrome.
TÍTULO / TITLE:
- Ohnologs in the human genome are dosage balanced and frequently associated with disease
RESUMEN / SUMMARY:
REVISTA / JOURNAL:
- PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, eFIRST date: 4 MAY 2010
AUTORES / AUTHORS:
- Makino, T; McLysaght, A
RESUMEN / SUMMARY:
- About 30% of protein-coding genes in the human genome are related through two whole genome duplication (WGD) events. Although WGD is often credited with great evolutionary importance, the processes governing the retention of these genes and their biological significance remain unclear. One increasingly popular hypothesis is that dosage balance constraints are a major determinant of duplicate gene retention. We test this hypothesis and show that WGD-duplicated genes (ohnologs) have rarely experienced subsequent small-scale duplication (SSD) and are also refractory to copy number variation (CNV) in human populations and are thus likely to be sensitive to relative quantities (i.e., they are dosage-balanced). By contrast, genes that have experienced SSD in the vertebrate lineage are more likely to also display CNV. This supports the hypothesis of biased retention of dosage-balanced genes after WGD. We also show that ohnologs have a strong association with human disease. In pa! rticular, Down Syndrome (DS) caused by trisomy 21 is widely assumed to be caused by dosage effects, and 75% of previously reported candidate genes for this syndrome are ohnologs that experienced no other copy number changes. We propose the remaining dosage-balanced ohnologs on chromosome 21 as candidate DS genes. These observations clearly show a persistent resistance to dose changes in genes duplicated by WGD. Dosage balance constraints simultaneously explain duplicate gene retention and essentiality after WGD.
TÍTULO / TITLE:
- On the paternal origin of trisomy 21 Down syndrome.
RESUMEN / SUMMARY:
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REVISTA / JOURNAL:
- Mol Cytogenet. 2010 Feb 23;3:4.
AUTORES / AUTHORS:
- Hulten MA; Patel SD; Westgren M; Papadogiannakis N; Jonsson AM; Jonasson J; Iwarsson E
INSTITUCIÓN / INSTITUTION:
- Warwick Medical School, University of Warwick, UK.
maj.hulten@warwick.ac.uk
RESUMEN / SUMMARY:
- ABSTRACT: BACKGROUND: Down syndrome (DS), characterized by an extra free chromosome 21 is the most common genetic cause for congenital malformations and learning disability. It is well known that the extra chromosome 21 originates from the mother in more than 90% of cases, the incidence increases with maternal age and there is a high recurrence in young women. In a previous report we have presented data to indicate that maternal trisomy 21 (T21) ovarian mosaicism might provide the major causative factor underlying these patterns of DS inheritance. One important outstanding question concerns the reason why the extra chromosome 21 in DS rarely originates from the father, i.e. in less than 10% of T21 DS cases. We here report data indicating that one reason for this parental sex difference is a very much lower degree of fetal testicular in comparison to ovarian T21 mosaicism. RESULTS: We used fluorescence in situ hybridisation (FISH) with two chromosome 21-specific probes to determine the copy number of chromosome 21 in fetal testicular cell nuclei from four male fetuses, following termination of pregnancy for a non-medical/social reason at gestational age 14-19 weeks. The cells studied were selected on the basis of their morphology alone, pending immunological specification of the relevant cell types. We could not detect any indication of testicular T21 mosaicism in any of these four male fetuses, when analysing at least 2000 cells per case (range 2038-3971, total 11.842). This result is highly statistically significant (p < 0.001) in comparison to the average of 0.54% ovarian T21 mosaicism (range 0.20-0.88%) that we identified in eight female fetuses analysing a total of 12.634 cells, as documented in a previous report in this journal. CONCLUSION: Based on these observations we suggest that there is a significant sex difference in degrees of fetal germ line T21 mosaicism. Thus, it would appear that most female fetuses are T21 ovarian mosaics, while in sharp contrast most male fetuses may be either very low grade T21 testicular mosaics or they may be non-mosaics. We further propose that this sex difference in germ line T21 mosaicism may explain the much less frequent paternal origin of T21 DS than maternal. The mechanisms underlying the DS cases, where the extra chromosome 21 does originate from the father, remains unknown and further studies in this respect are required.
TÍTULO / TITLE:
- A mouse model of Down syndrome trisomic for all human chromosome 21 syntenic regions.
RESUMEN / SUMMARY:
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REVISTA / JOURNAL:
- Hum Mol Genet. 2010 May 12.
AUTORES / AUTHORS:
- Yu T; Li Z; Jia Z; Clapcote SJ; Liu C; Li S; Asrar S; Pao A; Chen R; Fan N; Carattini-Rivera S; Bechard AR; Spring S; Henkelman RM; Stoica G; Matsui S
INSTITUCIÓN / INSTITUTION:
- Genetics Program and Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
RESUMEN / SUMMARY:
- Down syndrome (DS) is caused by the presence of an extra copy of human chromosome 21 (Hsa21) and is the most common genetic cause for developmental cognitive disability. The regions on Hsa21 are syntenically conserved with three regions located on mouse chromosome 10 (Mmu10), Mmu16 and Mmu17. In this report, we describe a new mouse model for DS that carries duplications spanning the entire Hsa21 syntenic regions on all three mouse chromosomes. This mouse mutant exhibits DS-related neurological defects, including impaired cognitive behaviors, reduced hippocampal long-term potentiation and hydrocephalus. These results suggest that when all the mouse orthologs of the Hsa21 genes are triplicated, an abnormal cognitively relevant phenotype is the final outcome of the elevated expressions of these orthologs as well as all the possible functional interactions among themselves and/or with other mouse genes. Because of its desirable genotype and phenotype, this mutant may have the potential to serve as one of the reference models for further understanding the developmental cognitive disability associated with DS and may also be used for developing novel therapeutic interventions for this clinical manifestation of the disorder.
TÍTULO / TITLE:
- Microdeletion of the Down syndrome critical region at 21q22.
RESUMEN / SUMMARY:
-
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REVISTA / JOURNAL:
- Am J Med Genet A. 2010 Apr;152ª(4):950-3.
AUTORES / AUTHORS:
- Fujita H; Torii C; Kosaki R; Yamaguchi S; Kudoh J; Hayashi K; Takahashi T; Kosaki K
INSTITUCIÓN / INSTITUTION:
- Division of Clinical Genetics and Molecular Medicine, National Center for Child Health and Development, Tokyo, Japan.
RESUMEN / SUMMARY:
- The concept of the Down syndrome critical region implies the existence of several dosage-sensitive genes that result in an abnormal phenotype when duplicated. Among the genes in the presumed Down syndrome critical region, DYRK1A and SIM2 are thought to be particularly important because of their critical roles in the development of the central nervous system in model organisms. Considering that regulatory imbalances resulting in an altered amount of expression from crucial target genes tend to produce phenotypic effects in both monosomics and trisomics, haploinsufficiency for the Down syndrome critical region is expected to be associated with an abnormal phenotype. We report on a patient with severe microcephaly, a developmental delay, hypospadias, and corneal opacity who had a microdeletion spanning the Down syndrome critical region, including DYRK1A and SIM2. He presented with intrauterine growth retardation, hypospadias, corneal clouding, arched eyebrows, upslanting and narrow palpebral fissures, bifid uvula, prominent nasal root, short columella, prominent central incisors, pegged shaped teeth, retrognathia, hypoplastic nipples, and severe developmental delay. His G-banded karyotype was normal, but array comparative genomic hybridization showed a de novo deletion of 3.97 Mb at chromosome 21q22. The extreme degree of microcephaly in this patient may be ascribed to the haploinsufficiency of DYRK1A, since brain size is severely reduced in heterozygotes for the Dyrk1a null mutation in mice.
TÍTULO / TITLE:
- Atypical Down syndrome phenotype in a girl with 21;21 translocation trisomy.
RESUMEN / SUMMARY:
-
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REVISTA / JOURNAL:
- Genet Couns. 2010;21(1):61-7.
AUTORES / AUTHORS:
- Tuysuz B; Yavuz A; Ozdil M; Caferler J; Ozon H
INSTITUCIÓN / INSTITUTION:
- Division of Genetics, Department of Pediatrics, Istanbul University, Cerrahpasa Faculty of Medicine, Istanbul, Turkey
beyhan@istanbul.edu.tr
RESUMEN / SUMMARY:
- We describe a girl with microcephaly, short stature, coarse face, severe growth and developmental delay, seizures, hypertonia, bilateral flexion contractures of the knees, and a de novo 21;21 translocation trisomy 21 in peripheral blood lymphocytes. Fluorescence in situ hybridization (FISH) analysis confirmed the trisomy 21 translocation using whole chromosome painting probe 21 (WCP21). Chromosome analysis which was also performed on skin fibroblasts and revealed mosaicism for a translocation trisomy 21 cell line (22.3%) as well as a second cell line consisting of one normal chromosome 21 and a small ring chromosome 21 derived from the translocation 21q21q (61%) and a third line consisting of monosomy 21 (16.7%). FISH analyses by LS121 probe for the critical (21q22.2-22.3) region of Down syndrome (DS) on interphase blood cells resulted with 30% two signals and 70% three signals, skin fibroblasts showed 84% single signal, 9% two signals and 7% three signals. The size of ring chromosome 21 in skin fibroblasts was very small and probably there was a large, more proximally located deletion including chromosome 21q22 band. We consider that the atypical DS phenotype of the patient originated from the small ring chromosome 21 and the monosomy 21 in the skin fibroblasts and other tissues not available for analysis. Therefore, the clinical findings of the patient were most similar to monosomy 21 mosaicism syndrome.
TÍTULO / TITLE:
- Trisomy 21: fifty years between medicine and science
RESUMEN / SUMMARY:
REVISTA / JOURNAL:
- M S-MEDECINE SCIENCES, 26 (3): 267-272 MAR 2010
AUTORES / AUTHORS:
- Turleau, C; Vekemans, M
RESUMEN / SUMMARY:
- Trisomy 21: fifty years between medicine and science
Fifty years after the discovery of the etiology of Down syndrome, trisomy 21 remains the model of choice for studying human diseases resulting from the presence of a chromosome or a chromosome segment in excess. In this review, mechanisms of aneuploidy occurrence and consequences of genomic imbalances will be mainly discussed. The study of genetic markers showed that trisomy 21 results in 90% of cases from an error during maternal meiosis. Approximately 8% of cases result from an error during paternal meiosis and in 2% of cases there is a postzygotic mitotic nondisjunction. The biological basis of the effect of maternal age remains largely unknown. The absence of genetic recombination between homologous chromosomes or the presence of an exchange in telomeric position are two risk factors of non-disjunction observed in young women. Non-disjunctions associated with pericentromeric exchanges are observed with an increase in maternal age. The study of mouse models and patient! s with partial trisomy 21, combined with advances in knowledge of the physical map and the transcriptome, identified genes directly or indirectly involved in the pathogenesis of Down syndrome. The recent description of metabolic pathways controlled by RCAN1 and DYRK1A genes which may be involved in many biological processes and phenotypes associated with trisomy 21 allows to consider new therapeutic strategies.
GROWTH/DEVELOPMENT - CRECIMIENTO/DESARROLLO
TÍTULO / TITLE:
- Co-occurrence of achondroplasia and Down syndrome: Genotype/phenotype association.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- Birth Defects Res A Clin Mol Teratol. 2010 Mar 10.
AUTORES / AUTHORS:
- de Azevedo Moreira LM; Matos MA; Schiper PP; Carvalho AF; Gomes IC; Rolemberg JC; de Lima RL; Toralles MB
INSTITUCIÓN / INSTITUTION:
- Laboratory of Human Genetics and Mutagenesis, Biology Institute, Federal University of Bahia, Salvador, Bahia, Brazil.
RESUMEN / SUMMARY:
- BACKGROUND: This report describes the sixth case of an unusual association: Down syndrome with achondroplasia. It also analyzes the effects of both of these disorders on patient phenotype. METHODS: A male infant was evaluated for Down syndrome. His appearance also suggested a diagnosis of achondroplasia. The child was evaluated by physical examination, radiography, cytogenetic study, and mutation analysis. RESULTS: Chromosome analysis showed a karyotype of 47,XY,+21 in all 30 cells analyzed. Radiographic examination showed typical findings of achondroplasia, such as disproportionately large skull, shortening oflimb segments, and lumbar lordosis. FGFR3 screening showed a heterozygous G1138A mutation. CONCLUSIONS: The interaction of these two distinct genetic disorders in the same patient produces a phenotype typical of each syndrome with some overlapping signs. This case represents de novo origin of two disorders that both may be parental-age related. Birth Defects Research.
TÍTULO / TITLE:
- Embryonic and not maternal trisomy causes developmental attenuation in the Ts65Dn mouse model for Down syndrome.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- Dev Dyn. 2010 Jun;239(6):1645-53.
AUTORES / AUTHORS:
- Blazek JD; Billingsley CN; Newbauer A; Roper RJ
INSTITUCIÓN / INSTITUTION:
- Department of Biology, Indiana University-Purdue University Indianapolis, Indianapolis, Indiana 46202, USA.
RESUMEN / SUMMARY:
- Trisomy 21 results in Down syndrome (DS) and causes phenotypes that may result from alterations of developmental processes. The Ts65Dn mouse is the most widely used genetic and phenotypic model for DS. We used over 1,500 offspring from Ts65Dn and two nontrisomic genetically similar control strains to investigate the influence of trisomy on developmental alterations and number of offspring. For the first time, we demonstrate gross developmental attenuation of Ts65Dn trisomic offspring at embryonic day (E) 9.5 and E13.5 and show that the major determinant of the developmental changes is segmental trisomy of the embryo and not the trisomic maternal uterine environment. Maternal alleles of nontrisomic genes linked to Pde6b may also influence the development of Ts65Dn offspring. Both developmental attenuation and the contribution of trisomic and nontrisomic genes are important components in the genesis of DS phenotypes.
TÍTULO / TITLE:
- Fetal trisomy 21 and the risk of preeclampsia
RESUMEN / SUMMARY:
REVISTA / JOURNAL:
- JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE, 23 (1): 55-59 JAN 2010
AUTORES / AUTHORS:
- Defant, J; Gambello, MJ; Monga, M; Langlois, PH; Noblin, SJ; Vidaeff, AC
RESUMEN / SUMMARY:
- Objective. Microchimerism has been investigated as a possible contributor to the pathophysiology of preeclampsia. Although trisomy 21 is associated with pronounced microchimerism, it has not been connected with an increased risk of preeclampsia. Our objective was to readdress the relationship between preeclampsia and trisomy 21 in a large population.
Methods. Using the Texas Birth Defects Registry for 1999-2003, a cohort of 2995 pregnancies with a trisomy 21 fetus was identified and compared with a control cohort of 1959 pregnancies with fetal isolated oral clefts. Chi-square test was used to estimate the significance of observed difference in the proportion of preeclampsia between groups. The interactive and confounding effects of covariates were examined by stratified analysis and the Mantel-Haenszel method.
Results. We observed 84 cases of preeclampsia in the trisomy 21 cohort (3.7%) and 111 cases in the oral cleft cohort (5.7%). The crude OR for having preeclampsia in relation to trisomy 21 was 0.63 (95% CI 0.47-0.85). The OR estimates remained the same after adjustment for confounders.
Conclusion. Pregnancies carrying a trisomy 21 fetus do not have an increased risk of preeclampsia. Besides epidemiologic significance, our data also have relevance for genetic counseling.
HEMATOLOGY/ONCOLOGY - HEMATOLOGÍA/ONCOLOGÍA
TÍTULO / TITLE:
- Down syndrome childhood acute lymphoblastic leukemia has a unique spectrum of sentinel cytogenetic lesions that influences treatment outcome: a report from the Children’s Oncology Group.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- Blood. 2010 May 4.
AUTORES / AUTHORS:
- Maloney KW; Carroll WL; Carroll AJ; Devidas M; Borowitz MJ; Martin PL; Pullen J; Whitlock JA; Willman CL; Winick NJ; Camitta BM; Hunger SP
INSTITUCIÓN / INSTITUTION:
- University of Colorado Denver School of Medicine and the Children’s Hospital, Aurora, CO;
RESUMEN / SUMMARY:
- Children with Down syndrome (DS) have a markedly increased risk of ALL and an inferior outcome. We reviewed data from 2811 children with ALL enrolled in COG P9900 that included prospective testing for the major sentinel cytogenetic lesions in childhood ALL: ETV6-RUNX1, TCF3-PBX1, BCR-ABL1, MLL translocations and trisomies of chromosomes 4 and 10. Eighty (3%) B-precursor ALL patients had DS. Age, gender, white blood cell count, and NCI risk group were similar between ALL patients with/without DS, but a significantly higher percentage of children with DS-ALL were white (91.2% vs. 76.4%, p=0.001). Children with DS-ALL had significantly lower rates of the favorable cytogenetic lesions ETV6-RUNX1 (2.5% vs. 24%, p<0.0001) and trisomies of chromosomes 4 and 10 (7.7% vs. 24%, p=0.0009). The five-year event-free (EFS) and overall survival (OS) were inferior in children with DS-ALL; 69.9+/-8.6% vs. 78.1+/-1.2% (p=0.078), and 85.8+/-6.5% vs. 90.0+/-0.9% (p=0.033). However, when children with MLL translocations, BCR-ABL1, ETV6-RUNX1 and trisomies 4 and 10 were excluded, the EFS and OS were similar for children with and without DS (EFS 68.0+/-9.3% vs. 70.5+/-1.9%, p=0.817; and OS 86.7+/-6.7% vs. 85.4+/-1.5%; p=0.852), both overall and when adjusted for race. DS-ALL displays a unique spectrum of biological subtypes with different frequencies of sentinel cytogenetic lesions having a large influence on outcome.
TÍTULO / TITLE:
- Hsa-mir-125b-2 is highly expressed in childhood ETV6/RUNX1 (TEL/AML1) leukemias and confers survival advantage to growth inhibitory signals independent of p53
RESUMEN / SUMMARY:
REVISTA / JOURNAL:
- LEUKEMIA, 24 (1): 89-96 JAN 2010
AUTORES / AUTHORS:
- Gefen, N; Binder, V; Zaliova, M; Linka, Y; Morrow, M; Novosel, A; Edry, L; Hertzberg, L; Shomron, N; Williams, O; Trka, J; Borkhardt, A; Izraeli, S
RESUMEN / SUMMARY:
- MicroRNAs (miRNAs) regulate the expression of multiple proteins in a dose-dependent manner. We hypothesized that increased expression of miRNAs encoded on chromosome 21 (chr 21) contribute to the leukemogenic function of trisomy 21. The levels of chr 21 miRNAs were quantified by qRT-PCR in four types of childhood acute lymphoblastic leukemia (ALL) characterized by either numerical (trisomy or tetrasomy) or structural abnormalities of chr 21. Suprisingly, high expression of the hsa-mir-125b-2 cluster, consisting of three miRNAs, was identified in leukemias with the structural ETV6/RUNX1 abnormality and not in ALLs with trisomy 21. Manipulation of ETV6/RUNX1 expression and chromatin immunoprecipitation studies showed that the high expression of the miRNA cluster is an event independent of the ETV6/RUNX1 fusion protein. Overexpression of hsa-mir-125b-2 conferred a survival advantage to Ba/F3 cells after IL-3 withdrawal or a broad spectrum of apoptotic stimuli through inhibit! ion of caspase 3 activation. Conversely, knockdown of the endogenous miR-125b in the ETV6/RUNX1 leukemia cell line REH increased apoptosis after Doxorubicin and Staurosporine treatments. P53 protein levels were not altered by miR-125b. Together, these results suggest that the expression of hsa-mir-125b-2 in ETV6/RUNX1 ALL provides survival advantage to growth inhibitory signals in a p53-independent manner. Leukemia (2010) 24, 89-96; doi:10.1038/leu.2009.208; published online 5 November 2009
TÍTULO / TITLE:
- Transient Abnormal Myelopoiesis Associated with Down Syndrome Presenting as Severe Hydrops Fetalis: A Case Report.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- Fetal Diagn Ther. 2010 Feb 16.
AUTORES / AUTHORS:
- Malin GL; Kilby MD; Velangi M
INSTITUCIÓN / INSTITUTION:
- School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, UK.
RESUMEN / SUMMARY:
- We present a case of transient abnormal myelopoiesis (TAM) presenting as non-immune fetal hydrops (NIHF). Hydrops fetalis (HF) is a condition associated with very high perinatal mortality, especially when no treatable cause, such as fetal anaemia, exists. In fetuses prior to 24 weeks with NIHF, a chromosomal anomaly is a common association. TAM is a leukaemic condition, almost entirely limited to children with Down syndrome. The presentation of TAM prenatally is unusual but cases may present ultrasonographically with NIHF and associated fetal hepatosplenomegaly. We report a case presenting in this manner with NIHF detected at 29 weeks’ gestation and discuss the subsequent diagnosis and management of in utero TAM.
TÍTULO / TITLE:
- Acute leukemias in children with Down syndrome.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- Hematol Oncol Clin North Am. 2010 Feb;24(1):19-34.
AUTORES / AUTHORS:
- Zwaan CM; Reinhardt D; Hitzler J; Vyas P
INSTITUCIÓN / INSTITUTION:
- Department of Pediatric Oncology/Hematology, Erasmus MC/Sophia Children’s Hospital, Dr Molewaterplein 60, Rotterdam, The Netherlands
c.m.zwaan@erasmusmc.nl
RESUMEN / SUMMARY:
- Children with Down syndrome have an increased risk for developing both acute myeloid as well as lymphoblastic leukemia. These leukemias differ in presenting characteristics and underlying biology when compared with leukemias occurring in non-Down syndrome children. Myeloid leukemia in children with Down syndrome is preceded by a preleukemic clone (transient leukemia or transient myeloproliferative disorder), which may disappear spontaneously, but may also need treatment in case of severe symptoms. Twenty percent of children with transient leukemia subsequently develop myeloid leukemia. This transition offers a unique model to study the stepwise development of leukemia and of gene dosage effects mediated by aneuploidy.
TÍTULO / TITLE:
- Perturbed hematopoiesis in the Tc1 mouse model of Down Syndrome.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- Blood. 2010 Feb 12.
AUTORES / AUTHORS:
- Alford K; Slender A; Vanes L; Li Z; Fisher EM; Nizetic D; Orkin SH; Roberts I; Tybulewicz VL
INSTITUCIÓN / INSTITUTION:
- Division of Immune Cell Biology, MRC National Institute for Medical Research, London, United Kingdom;
RESUMEN / SUMMARY:
- Trisomy of human chromosome 21 (Hsa21) results in Down Syndrome (DS), a disorder that affects many aspects of physiology, including hematopoiesis. DS children have greatly increased rates of acute lymphoblastic leukemia and acute megakaryoblastic leukemia (AMKL); DS newborns present with Transient Myeloproliferative Disorder (TMD), a pre-leukemic form of AMKL. TMD and DS-AMKL almost always carry an acquired mutation in GATA1 resulting in exclusive synthesis of a truncated protein (GATA1s), suggesting that both trisomy 21 and GATA1 mutations are required for leukemogenesis. To gain further understanding of how Hsa21 contributes to hematopoietic abnormalities we examined the Tc1 mouse model of DS, which carries an almost complete freely segregating copy of Hsa21, and is the most complete model of DS available. We show that while Tc1 mice do not develop leukemia, they have macrocytic anemia and increased extramedullary hematopoiesis. Introduction of GATA1s into Tc1 mice resulted in a synergistic increase in megakaryopoiesis, but did not result in leukemia or a TMD-like phenotype, demonstrating that GATA1s and trisomy of ~80% of Hsa21 perturb megakaryopoiesis but are insufficient to induce leukemia.
TÍTULO / TITLE:
- Mosaic Down syndrome-associated acute myeloid leukemia does not require high-dose cytarabine treatment for induction and consolidation therapy.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
-
AUTORES / AUTHORS:
- Kudo K; Hama A; Kojima S; Ishii R; Morimoto A; Bessho F; Sunami S; Kobayashi N; Kinoshita A; Okimoto Y; Tawa A; Tsukimoto I
INSTITUCIÓN / INSTITUTION:
- Division of Hematology and Oncology, Shizuoka Children’s Hospital, 860, Urushiyama, Aoi-ku, Shizuoka, 420-8660, Japan
kazukok@sch.pref.shizuoka.jp
RESUMEN / SUMMARY:
- The present study aimed to identify optimal treatment intensity in children with mosaic Down syndrome (DS) and acute megakaryoblastic leukemia (AMKL). A retrospective review of AMKL patients was undertaken to identify mosaic DS children. Between November 1992 and November 2007, seven children were diagnosed as mosaic DS and AMKL. The median age at diagnosis was 29 months (range 4-34 months). Three patients had a past history of transient abnormal myelopoiesis. UPN1-4 were treated with intermediate-dose cytarabine and UPN4 received additional one course of high-dose cytarabine. All of these patients were remained in first CR. UPN5-7 were treated with high-dose cytarabine according to the AML99 protocol. UPN5 with GATA1 mutation suffered from acute pneumonia and pancreatitis and discontinued chemotherapy. UPN7 relapsed after cessation of chemotherapy and was rescued with allo-PBSCT. The cumulative doses of cytarabine were 3.5-10.65 g/m(2) in the UPN1-4 and 40.4-78.4 g/m(2) in the UPN5-7. The 8-year overall survival was 100% and the 8-year event-free survival 85.7%, respectively. Our retrospective study reveals that patients with mosaic DS and AMKL have a good prognosis. Reduction in intensity may work in patients with mosaic DS as well as with AML-DS.
TÍTULO / TITLE:
- Acute myeloid leukemia with del(X)(p21) and cryptic RUNX1/RUNX1T1 from ins(8;21)(q22;q22q22) revealed by atypical FISH signals.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- Ann Clin Lab Sci. 2010 Winter;40(1):80-4.
AUTORES / AUTHORS:
- Jang JH; Yoo EH; Kim HJ; Kim DH; Jung CW; Kim SH
INSTITUCIÓN / INSTITUTION:
- Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
RESUMEN / SUMMARY:
- A 57-yr-old woman was diagnosed with acute myeloid leukemia (AML) with maturation, based on morphological and cytochemical/immunophenotypic findings on bone marrow studies. Conventional cytogenetic analysis using bone marrow cells revealed terminal deletion of the short arm of an X chromosome as 46,X,del(X)(p21)[8]/46,XX[12]. On the other hand, fluorescence in situ hybridization (FISH) for the RUNX1/RUNX1T1 (formerly AML1/ETO) rearrangement revealed 86% interphase nuclei with one fusion signal, which was found to be on the long arm of chromosome 8 on metaphase FISH, indicating the RUNX1/RUNX1T1 rearrangement by cryptic insertion of the RUNX1 gene. Molecular genetic study by reverse transcriptase polymerase chain reaction (RT-PCR) confirmed the presence of the chimeric transcript. The final karyotype was 46,X,del(X)(p21).ish ins(8;21)(q22;q22q22)(RUNX1T1+,RUNX1+;RU NX1+,RUNX1T1-)[8]/46,XX[12]. In addition to the cryptic RUNX1/RUNX1T1 rearrangement, this is the first report of partial deletion of an X chromosome as an additional cytogenetic aberration in AML with RUNX1/RUNX1T1.
TÍTULO / TITLE:
- Functional differences between myeloid leukemia-initiating and transient leukemia cells in Down’s syndrome.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- Leukemia. 2010 Mar 11.
AUTORES / AUTHORS:
- Chen J; Li Y; Doedens M; Wang P; Shago M; Dick J; Hitzler JK
INSTITUCIÓN / INSTITUTION:
- Developmental and Stem Cell Biology, The Hospital for Sick Children Research Institute, Toronto, Ontario, Canada.
RESUMEN / SUMMARY:
- Children with constitutional trisomy 21 or Down’s syndrome (DS) are predisposed to develop myeloid leukemia (ML) at a young age. DS-ML is frequently preceded by transient leukemia (TL), a spontaneously resolving accumulation of blasts during the newborn period. Somatic mutations of GATA1 in the blasts of TL and DS-ML likely function as an initiating event. We hypothesized that the phenotypic difference between TL and DS-ML is due to a divergent functional repertoire of the leukemia-initiating cells. Using an NOD/SCID model, we found that cells initiating DS-ML engrafted, disseminated to distant bone marrow sites, and propagated the leukemic clone in secondary recipients. In contrast, TL cells lacked the ability to expand and to migrate, but were able to persist in the recipient bone marrow. We found some evidence of genomic progression with 1 of 9 DS-ML samples and none of 11 TL samples harboring a mutation of N-RAS. The findings of this pilot study provide evidence for the functional impact of second events underlying the transformation of TL into DS-ML and a needed experimental tool for the functional testing of these promoting events.Leukemia advance online publication, 11 March 2010; doi:10.1038/leu.2010.30.
TÍTULO / TITLE:
- Fatal Neurotoxicity in a Patient With Down Syndrome Treated With Chemotherapy, Irradiation, Stem Cell Transplant, and Clofarabine.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- J Pediatr Hematol Oncol. 2010 Mar 1.
AUTORES / AUTHORS:
- Johnston DL; Bains T; Mandel K; Klaassen R; Halton J
INSTITUCIÓN / INSTITUTION:
- *Division of Hematology/Oncology daggerDepartment of Pharmacy, Children’s Hospital of Eastern Ontario, Ottawa, Ontario, Canada.
RESUMEN / SUMMARY:
- Clofarabine is an effective therapy of pediatric patients with relapsed acute lymphoblastic leukemia (ALL). We present a child with Down syndrome who had received previous chemotherapy, cranial radiation, and a stem cell transplant with total body irradiation for her acute lymphoblastic leukemia. She subsequently relapsed and was treated with clofarabine. After her third course, she had a stroke that was felt to be secondary to dehydration and radiation vasculitis. After her subsequent course of clofarabine, she developed fatal neurotoxicity.
TÍTULO / TITLE:
- Methotrexate induced side effects are not due to differences in pharmacokinetics in children with Down syndrome and acute lymphoblastic leukemia.
RESUMEN / SUMMARY:
-
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REVISTA / JOURNAL:
- Haematologica. 2010 Apr 23.
AUTORES / AUTHORS:
- Buitenkamp TD; Mathot RA; de Haas V; Pieters R; Zwaan CM
INSTITUCIÓN / INSTITUTION:
- Rotterdam, the Netherlands;
RESUMEN / SUMMARY:
- Background. Children with Down Syndrome (DS) have an increased risk of developing acute lymphoblastic leukemia (ALL). They have a poor tolerance for methotrexate (MTX). This is assumed to be caused by a higher cellular sensitivity of the tissues in DS children. However, whether differences in pharmacokinetics (PK) play a role is unknown. Design and Methods. We compared MTX induced toxicity and pharmacokinetics in a retrospective case-control study between DS-ALL and non-DS ALL patients. Population PK-models were fitted to data from all individuals simultaneously, using non-linear mixed effect modeling. Results. 468 MTX courses (1-5 g/m2) were given to 44 DS and 87 non-DS ALL patients. Grade 3-4 gastro-intestinal toxicity was significantly more frequent in DS versus non-DS children (25.5% vs. 3.9%; p=0.001). Moreover, the occurrence of grade 3-4 gastro-intestinal toxicity was not related to plasma MTX area under the curve (AUC). MTX-clearance was 5% lower in DS-ALL patients (p= 0.001), however this small difference is probably clinically not relevant, because no significant differences in MTX plasma levels were detected at T=24 and at T=48 hours. Conclusions. We did not find evidence for differences in MTX pharmacokinetics between DS and non-DS patients which explained the higher frequency of gastrointestinal toxicity and the greater need for MTX dose reductions. Hence, these differences are most likely explained by differential pharmacodynamic effects in the tissues between DS and non-DS children. Although the number of patients is limited, we feel that it may be safe to start with intermediate dosages of MTX (1-3 gr/m2), followed by careful monitoring.
TÍTULO / TITLE:
- Cytokine profiles before and after exchange transfusion in a neonate with transient myeloproliferative disorder and hepatic fibrosis.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- J Pediatr Hematol Oncol. 2010 May;32(4):e164-6.
AUTORES / AUTHORS:
- Sugiura T; Goto K; Ninchoji T; Aiba K; Kouwaki M; Koyama N; Togari H
INSTITUCIÓN / INSTITUTION:
- Department of Pediatrics and Neonatology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan.
sugitoki23@yahoo.co.jp
RESUMEN / SUMMARY:
- SUMMARY: To study the effect of exchange transfusion on cytokine profiles in a patient with transient myeloproliferative disorder and hepatic fibrosis in which cytokines were measured before and after exchange transfusion. A newborn female was diagnosed with Down syndrome phenotypically and on karyotyping. Laboratory data showed a high leukocyte count with blast cells in the peripheral blood and liver dysfunction. Exchange transfusion was performed on day 1. However, respiratory distress and multiorgan failure progressed, and she died after 16 days. Of the cytokines examined, transforming growth factor-beta1 and interleukin-7 were extremely high before exchange transfusion, and decreased after exchange transfusion.
TÍTULO / TITLE:
- Perturbed hematopoiesis in the Tc1 mouse model of Down syndrome
RESUMEN / SUMMARY:
REVISTA / JOURNAL:
- BLOOD, 115 (14): 2928-2937 APR 8 2010
AUTORES / AUTHORS:
- Alford, KA; Slender, A; Vanes, L; Li, Z; Fisher, EMC; Nizetic, D; Orkin, SH; Roberts, I; Tybulewicz, VLJ
RESUMEN / SUMMARY:
- Trisomy of human chromosome 21 (Hsa21) results in Down syndrome (DS), a disorder that affects many aspects of physiology, including hematopoiesis. DS children have greatly increased rates of acute lymphoblastic leukemia and acute megakaryoblastic leukemia (AMKL); DS newborns present with transient myeloproliferative disorder (TMD), a preleukemic form of AMKL. TMD and DS-AMKL almost always carry an acquired mutation in GATA1 resulting in exclusive synthesis of a truncated protein (GATA1s), suggesting that both trisomy 21 and GATA1 mutations are required for leukemogenesis. To gain further understanding of how Hsa21 contributes to hematopoietic abnormalities, we examined the Tc1 mouse model of DS, which carries an almost complete freely segregating copy of Hsa21, and is the most complete model of DS available. We show that although Tc1 mice do not develop leukemia, they have macrocytic anemia and increased extramedullary hematopoiesis. Introduction of GATA1s into Tc1 mice r! esulted in a synergistic increase in megakaryopoiesis, but did not result in leukemia or a TMD-like phenotype, demonstrating that GATA1s and trisomy of approximately 80% of Hsa21 perturb megakaryopoiesis but are insufficient to induce leukemia. (Blood. 2010;115(14):2928-2937)
TÍTULO / TITLE:
- Acute myeloid leukemia (AML-M2) associated with variant t(8;21): report of three cases.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- Cancer Genet Cytogenet. 2010 May;199(1):31-7.
AUTORES / AUTHORS:
- Bae SY; Kim JS; Ryeu BJ; Lee KN; Lee CK; Kim YK; Lim CS; Cho Y; Choi CW; Ryu SW; Yoon SY
INSTITUCIÓN / INSTITUTION:
- Department of Laboratory Medicine, Korea University College of Medicine, Seongbuk-Gu, Seoul, Republic of Korea.
RESUMEN / SUMMARY:
- Variants of the t(8;21)(q22;q22) involving chromosome 8, 21, and other chromosomes account for approximately 3% of all t(8;21)(q22;q22) found in patients with acute myeloid leukemia (AML). The clinicopathologic features of AML with the variant t(8;21) have not been well established. We report three cases of AML with variants of t(8;21) characterized, respectively, by derivative 8 with the interstitial inverted insertion of 21q and concurrent monosomy 21, t(8;18;21)(p22;q11.3;q22), and t(2;21;8)(q11.2;q22;q22). Fluorescence in situ hybridization or reverse transcriptase-polymerase chain reaction assay confirmed the presence of RUNX1-RUNX1T1 gene (previously AML1-ETO) rearrangements. Among these cases, three-way breakpoints 18p11.3 and 2q11.2 have not been previously reported. The present report deals with the results of hematologic, immunophenotypic, cytogenetic, fluorescence in situ hybridization, and molecular analyses of these variants. The possible role of the genes in this region in leukemogenesis, response to treatment, and clinical implications are discussed.
TÍTULO / TITLE:
- Myeloid proliferation without GATA1 mutations in a fetus with Down syndrome presenting in utero as a pericardial effusion.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- Pediatr Dev Pathol. 2010 Apr 29.
AUTORES / AUTHORS:
- Rougemont AL; Makrythanasis P; Finci V; Billieux MH; Epiney M; McKee TA; Nizetic D; Fokstuen S
INSTITUCIÓN / INSTITUTION:
- 1 Hopitaux Universitaires de Geneve.
RESUMEN / SUMMARY:
- Abstract An isolated pericardial effusion was observed during a routine prenatal ultrasound in a fetus of 30 3/7 weeks gestation. Amniocentesis was performed and revealed a trisomy 21. After prenatal counseling, the parents opted for termination of the pregnancy at 32 weeks. Post-mortem examination confirmed the presence of a pericardial effusion, without structural cardiac anomalies, and showed the development of ascites and subcutaneous edema. Histological examination showed an infiltrate of megakaryoblasts and irregular, dysplastic megakaryocytes confined to the epicardium, the pericardial lymph nodes, and the pancreas, consistent with a myeloid proliferation related to Down syndrome. Sequencing of exons 2 and 3 of the GATA1 gene from the umbilical cord blood and from megakaryoblast infiltrate showed no mutation. A high incidence of chromosomal abnormalities, in particular trisomy 21 has been described in fetuses with pericardial effusion. However, myeloid proliferation related to Down syndrome without GATA1 mutations is extremely rare. To our knowledge, only one such case has been reported to date. We present here a second case which further supports the hypothesis that hyperproliferation of megakaryocytes in a subset of Down syndrome patients may be initiated by events other than GATA1 mutations.
TÍTULO / TITLE:
- Coeliac disease as the cause of resistant sideropenic anaemia in children with Down’s syndrome: case report.
RESUMEN / SUMMARY:
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Enlace al Resumen
REVISTA / JOURNAL:
- Srp Arh Celok Lek. 2010 Jan-Feb;138(1-2):91-4.
AUTORES / AUTHORS:
- Pavlovic M; Radlovic N; Lekovic Z; Berenji K; Stojsic Z; Radlovic V
INSTITUCIÓN / INSTITUTION:
- Paediatric Department, General Hospital, Subotica, Serbia.
momodec@tippnet.rs
RESUMEN / SUMMARY:
- INTRODUCTION: Coeliac disease (CD) is a permanent intolerance of gluten, i.e., of gliadin and related proteins found in the endosperm of wheat, rye and barley. It is characterized by polygenic predisposition, autoimmune nature, predominantly asymptomatic or atypical clinical course, as well as by high prevalence in patients with Down’s syndrome (DS) and some other diseases. OUTLINE OF CASES: We are presenting a girl and two boys, aged 6-7 (x = 6.33) years with DS and CD recognized under the feature of sideropenic anaemia resistant to oral therapy with iron. Beside mental retardation, low stature and the morphological features characteristic of DS, two patients had a congenital heart disease; one ventricular septal defect and the other atrioventricular canal. In two patients, trisomy on the 21st chromosome pair (trisomy 21) was disclosed in all cells, while one had a mosaic karyotype. All three patients had classical laboratory parameters of sideropenic anaemia: blood Hb 77-89 g/l (x = 81.67), HCT 0.26-0.29% (x = 0.28), MCV 69-80 fl (x = 73), MCH 24.3-30 pg (x = 26.77) and serum iron 2-5 micromol/L (x = 4.0). Beside anaemia and in one patient a mild isolated hypertransaminasemia (AST 67 U/l, ALT 62 U/l), other indicators of CD were not registered in any of the children. In addition, in all three patients, we also detected an increased level of antibodies to tissue transglutaminase (atTG) of IgA class (45-88 U/I) so that we performed endoscopic enterobiopsy in order to reliably confirm the diagnosis of CD. In all three patients, the pathohistological finding of the duodenal mucosa specimen showed mild to moderate destructive enteropathy associated with high intraepithelial lymphocyte infiltration, cryptic hyperplasia and lympho-plasmocytic infiltration of the stroma. In all three patients, the treatment with a strict gluten-free diet and iron therapy applied orally for 3-4 months resulted in blood count normalization and the correction of sideropenia. Serum level of the atTG-IgA, repeated after a 12-month diet, was also normal. CONCLUSION: CD should be taken into consideration in all cases of sideropenic anaemia resistant to iron oral therapy in children with DS.The diagnosis of CD implicates corresponding pathohistological confirmation, while the treatment of sideropenic anaemia and its complications, beside iron preparations, also requires compliance with a gluten-free diet.
TÍTULO / TITLE:
- Myeloid leukaemia in children with Down syndrome: report of the registry-based French experience between 1990 and 2003.
RESUMEN / SUMMARY:
-
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REVISTA / JOURNAL:
- Pediatr Blood Cancer. 2010 Jul 1;54(7):927-33.
AUTORES / AUTHORS:
- Tandonnet J; Clavel J; Baruchel A; Nacka F; Perel Y
INSTITUCIÓN / INSTITUTION:
- Bordeaux University and Bordeaux University Hospital, Pediatric Oncology and Hematology Unit, 33076 Bordeaux, France.
RESUMEN / SUMMARY:
- AIM: To determine the epidemiology of myeloid leukaemia (ML) in children with Down syndrome (DS) and the efficacy of two approaches, low-dose cytarabine-based regimen (LDC) and standard-dose intensive chemotherapy (SD). PROCEDURE: All children with Down syndrome aged from 2 months to 15 years with ML/myelodysplasia registered in the French registry between January 1990 and December 2003 were included. RESULTS: Forty-four patients were included. The median age was 1.75 years. The French-America-British subtypes were as follows: M7: 24, M0: 6, M2: 5, M6: 2. Forty-three patients were treated with curative prospect, 20 patients with LDC regimen and 22 according to SD protocols, 1 was given the LDC regimen plus autologous stem-cell transplantation. The event-free survival (EFS) and overall survival (OS) at 5 years were 64.4% and 76.8%. At 5 years, OS in LDC and SD groups were 65% and 85.9% (P = 0.08). EFS were 45% and 80.3% respectively (P < 0.01). CONCLUSION: Children with DS can adequately tolerate SD chemotherapy with a significant superiority of EFS relative to LDC. We suggest that higher levels of cure can be obtained in DS-ML with SD chemotherapy including cytarabine and anthracyclines.
INFECTIOUS DISEASES - INFECCIONES
TÍTULO / TITLE:
- Intestinal barrier gene variants may not explain the increased levels of antigliadin antibodies, suggesting other mechanisms than altered permeability
RESUMEN / SUMMARY:
REVISTA / JOURNAL:
- HUMAN IMMUNOLOGY, 71 (4): 392-396 APR 2010
AUTORES / AUTHORS:
- Wolters, VM; Alizadeh, BZ; Weijerman, ME; Zhernakova, A; van Hoogstraten, IMW; Mearin, ML; Wapenaar, MC; Wijmenga, C; Schreurs, MWJ
RESUMEN / SUMMARY:
- Various genes may influence intestinal barrier function, including MAGI2, MY09B, and PARD3, which are associated with celiac disease. Because direct measurement of intestinal permeability is difficult, antibodies against gliadin (AGA) and Baker`s yeast (anti-Saccharomyces cerevisiae antibodies [ASCA]) can be used as an indirect test. The objective of this study was to investigate whether intestinal permeability, represented by AGA, was correlated with MAGI2, MY09B, and PARD3. Analyses were performed in patients with Down syndrome, a population with suspected increased intestinal permeability. Correlations between AGA and ASCA were investigated. Patients with Down syndrome (n = 126) were genotyped for six single-nucleotide polymorphisms in MAGI2 (rs1496770, rs6962966, rs9640699), MY09B (rs1457092, rs2305764), and PARD3 (rs10763976). An allele dosage association of these risk genes and AGA levels was performed. The correlation between AGA and ASCA was studied. A strong corr! elation was found between AGA and ASCA (p < 0.01). The patient group with one or more risk genotypes had lower mean AGA levels (trend test p = 0.007) and consisted of a larger number of patients with normal AGA levels (p = 9.3 x 10(-5)). Celiac-associated risk genotypes are associated with lower AGA values instead of elevated ones. Thus, other immunologic phenomena play a role in the increased prevalence of elevated AGA in patients with Down syndrome, possibly involving altered induction and/or maintenance of tolerance.
TÍTULO / TITLE:
- DOWN SYNDROME AND RESPIRATORY SYNCYTIAL VIRUS INFECTION.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- Pediatr Infect Dis J. 2010 Mar 11.
AUTORES / AUTHORS:
- Megged O; Schlesinger Y
INSTITUCIÓN / INSTITUTION:
- From the Department of Pediatrics and Infectious Diseases Unit, Shaare Zedek Medical Center, Jerusalem, affiliated with the Hadassah-Hebrew University Medical School, Jerusalem, Israel.
RESUMEN / SUMMARY:
- We reviewed the medical records of all children with Down syndrome (DS), hospitalized in our medical center due to infection with respiratory syncytial virus. During the 9-year study period, there were 41 hospitalizations of 39 children with DS. Mean age was 1.3 years; mean duration of hospitalization was 10.9 days. Patients with DS were older than healthy controls with respiratory syncytial virus infection and needed longer hospitalization.
TÍTULO / TITLE:
- Distinct Abnormalities in the Innate Immune System of Children with Down Syndrome.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- J Pediatr. 2010 Feb 19.
AUTORES / AUTHORS:
- Bloemers BL; van Bleek GM; Kimpen JL; Bont L
INSTITUCIÓN / INSTITUTION:
- Department of Pediatrics, Division of Infectious Diseases and Immunology, University Medical Centre Utrecht, Utrecht, The Netherlands.
RESUMEN / SUMMARY:
- OBJECTIVE: To analyze the frequency and phenotype of cells of the innate immune system in the peripheral blood of children with Down syndrome (DS). STUDY DESIGN: Flow cytometric analysis of expression of cell surface markers was performed in children with DS (n = 41) and healthy age-matched controls (n = 41). RESULTS: Compared with controls, children with DS had significantly lower absolute total leukocyte counts, lymphocytes, monocytes, and granulocytes, but 1.5-times higher absolute numbers of CD14(dim)CD16(+) monocytes (147 x 10(6)/L vs 93 x 10(6)/L; P = .02). This difference is fully explained by a higher percentage of CD14(dim)CD16(+) monocytes within the monocyte compartment (28.7% vs 13.4%; P <.001). The absolute numbers of myeloid dendritic cells were lower in DS (13.8 x 10(6)/L vs 22.7 x 10(6)/L; P <.001). The numbers of plasmacytoid dendritic cells and natural killer cells were normal. Absolute numbers of invariant natural killer T cells were very low overall, but significantly lower in children with DS than in controls (1.2 x 10(6)/L vs 3.7 x 10(6)/L; P = .01). CONCLUSIONS: Children with DS exhibited distinct abnormalities in cells of the innate immune system. Most strikingly, they had a high number of proinflammatory CD14(dim)CD16(+) monocytes. This elevated level of CD14(dim)CD16(+) monocytes may play an important role in the onset and maintenance of chronic inflammatory disease in DS.
TÍTULO / TITLE:
- Analysis of peripheral blood T-cell subsets, natural killer cells and serum levels of cytokines in children with Down syndrome
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- Int J Immunogenet. 2010 Apr 30.
AUTORES / AUTHORS:
- Cetiner S; Demirhan O; Inal TC; Tastemir D; Sertdemir Y
INSTITUCIÓN / INSTITUTION:
- Central Laboratory of Balcali Hospital, Faculty of Medicine, University of Cukurova, Adana, Turkey.
RESUMEN / SUMMARY:
- Summary The objective of this study was to evaluate the relationship between humoral and cell-mediated immune response parameters and impairment of immune functions in children with Down syndrome (DS). The patient group was consisted of cytogenetically documented 32 children with DS. Lymphocyte subsets and natural killer cells were counted by flow-cytometry system. Levels of interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-8, IL-10 and tumour necrosis factor-alpha (TNF-alpha) were detected by enzyme-linked immunosorbent assay method. Serum IgG, IgM, IgA levels were measured by turbidimetric methods. The percentage of CD8+ lymphocytes and CD56+ cells of patients with DS were significantly higher, whereas CD20+ lymphocytes were lower than that of controls (P < 0.05). The percentage of CD2 and CD4 levels and CD4/CD8 ratio of patients with DS and normal controls were similar (P > 0.05). Levels of IL-4 and IL-10 were significantly increased, but IL-6 and TNF-alpha levels were decreased in children with DS (P < 0.05). Levels of other studied cytokines between patients with DS and controls were not statistically different (P > 0.05, for all). Serum IgG, IgM and IgA levels were found to be similar between the groups (P > 0.05). It has been known that IL-4 and IL-10 are anti-inflammatory molecules which inhibit the synthesis of proinflammatory cytokines such as IL-6 and TNF-alpha. In this study, levels of IL-4 and IL-10 were significantly increased, but IL-6 and TNF-alpha levels were decreased in children with DS. These results may suggest that continuing anti-inflammatory state in DS and this process may explain the cause of recurrent infection of the disease. On the other hand, in contrast to the low percentage of CD20+ cells, high percentage of CD8+ and CD56+ cells were found. Our findings may demonstrate that the cell-mediated and humoral immune system parameters in children with DS were altered according to healthy children.
MOLECULAR BIOLOGY/BIOCHEMISTRY - BIOLOGÍA MOLECULAR/BIOQUÍMICA
TÍTULO / TITLE:
- Melatonin and elimination of kynurenines in children with Down’s syndrome.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- J Pediatr Endocrinol Metab. 2010 Mar;23(3):277-82.
AUTORES / AUTHORS:
- Uberos J; Romero J; Molina-Carballo A; Munoz-Hoyos A
INSTITUCIÓN / INSTITUTION:
- Departamento de Pediatria, Facultad de Medicina, Universidad Granada, España.
uberosfernandez@terra.es
RESUMEN / SUMMARY:
- BACKGROUND: Heightened activity of superoxide dimutase is an effect derived from the gene dose in the trisomy of Down’s syndrome (DS), and has been related to the increased production of hydrogen peroxide and with greater lipid peroxidation. Many of the degenerative changes observed in patients with DS have been associated with the pathological effects of free radicals, and for this reason it is of interest to determine the levels present in these patients of powerful antioxidant molecules such as melatonin, and of metabolites with important neuroprotector and neurotoxic consequences such as those derived from the kynurenine pathway. PATIENTS AND METHODS: A study was made of 15 children with DS, together with a control group of 15 non-DS children, matched for age and sex, examined at the Hospital Costa del Sol, Marbella, España. Serum melatonin and serotonin were analyzed by RIA; urinary tryptophan metabolites (kynurenine pathway) were determined during periods of light and darkness (09.00-21.00 h and 21.00-9.00 h) by thin-layer chromatography. RESULTS: The mean values of serotonin and melatonin were found to be lower in the patients with DS, although the level of nocturnal secretion of melatonin was higher. Urinary excretion of kynurenine was lower in the patients with DS, although greater quantities of kynurenic acid and anthranilic acid were excreted. CONCLUSIONS: Patients with DS present levels of plasma melatonin and urinary kynurenine that are lower than the corresponding levels in the control population, together with higher values of kynurenic acid and anthranilic acid. These circumstances constitute an added risk to these patients of damage by free radicals.
TÍTULO / TITLE:
- Mitochondrial dysfunction in some oxidative stress-related genetic diseases: Ataxia-Telangiectasia, Down Syndrome, Fanconi Anaemia and Werner Syndrome.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- Biogerontology. 2010 Mar 18.
AUTORES / AUTHORS:
- Pallardo FV; Lloret A; Lebel M; d’Ischia M; Cogger VC; Le Couteur DG; Gadaleta MN; Castello G; Pagano G
INSTITUCIÓN / INSTITUTION:
- Department of Physiology, University of Valencia, CIBERER, 46010, Valencia, España.
RESUMEN / SUMMARY:
- Oxidative stress is a phenotypic hallmark in several genetic disorders characterized by cancer predisposition and/or propensity to premature ageing. Here we review the published evidence for the involvement of oxidative stress in the phenotypes of Ataxia-Telangiectasia (A-T), Down Syndrome (DS), Fanconi Anaemia (FA), and Werner Syndrome (WS), from the viewpoint of mitochondrial dysfunction. Mitochondria are recognized as both the cell compartment where energetic metabolism occurs and as the first and most susceptible target of reactive oxygen species (ROS) formation. Thus, a critical evaluation of the basic mechanisms leading to an in vivo pro-oxidant state relies on elucidating the features of mitochondrial impairment in each disorder. The evidence for different mitochondrial dysfunctions reported in A-T, DS, and FA is reviewed. In the case of WS, clear-cut evidence linking human WS phenotype to mitochondrial abnormalities is lacking so far in the literature. Nevertheless, evidence relating mitochondrial dysfunctions to normal ageing suggests that WS, as a progeroid syndrome, is likely to feature mitochondrial abnormalities. Hence, ad hoc research focused on elucidating the nature of mitochondrial dysfunction in WS pathogenesis is required. Based on the recognized, or reasonably suspected, role of mitochondrial abnormalities in the pathogenesis of these disorders, studies of chemoprevention with mitochondria-targeted supplements are warranted.
TÍTULO / TITLE:
- Homocysteine and oxidative stress in Egyptian children with Down syndrome.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- Clin Biochem. 2010 May 5.
AUTORES / AUTHORS:
- Meguid NA; Dardir AA; El-Sayed EM; Ahmed HH; Hashish AF; Ezzat A
INSTITUCIÓN / INSTITUTION:
- Research on Children with Special Needs Dept., National Research Centre, Egypt
RESUMEN / SUMMARY:
- OBJECTIVE: To assess homocysteine, folic acid and vitamin B(12), trace element levels and oxidant/antioxidant status in Down syndrome (DS) mothers and children. DESIGN AND METHODS: 42 mothers with previous history of bearing DS baby with karyotypically confirmed full trisomy 21 were included. 48 healthy mothers with their healthy children were considered as control. Serum B(12), folic acid, total homocysteine (tHcy), vitamins E and C, TBARS and trace elements were estimated. RESULTS: DS mothers showed higher levels of tHCy, lower levels of folic acid and vitamin B(12) than controls. tHCy and folic acid concentrations were significantly decreased, while vitamin B(12) exhibited a slight decrease in DS children versus control. Vitamins E and C, zinc and copper levels were markedly reduced in DS mothers. By contrast, TBARS showed significant elevation in them. Furthermore, DS children had severe reduction of vitamin C and zinc levels relative to healthy children. However, vitamin E showed slight reduction and TBARS displayed a slight rise in DS children. CONCLUSION: Abnormal folic acid-homocysteine metabolism is a potent marker to identify women at risk for having DS child and it also exposes them to oxidant/antioxidant imbalance.
TÍTULO / TITLE:
- Trisomy 21-affected placentas highlight prerequisite factors for human trophoblast fusion and differentiation
RESUMEN / SUMMARY:
REVISTA / JOURNAL:
- INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY, 54 (2-3): 475-482 Sp. Iss. SI 2010
AUTORES / AUTHORS:
- Malassine, A; Frendo, JL; Evain-Brion, D
RESUMEN / SUMMARY:
- Trophoblastic cell fusion is one essential step of the human trophoblast differentiation pathway and is a multifactorial and dynamic process finely regulated and still poorly known. Disturbances of syncytiotrophoblast formation are observed in numerous pathological clinical conditions such as preeclampsia, intrauterine growth retardation and trisomy 21. In this review, we summarize current knowledge of the different membrane proteins directly involved in trophoblastic cell fusion, which we identified by using the physiological model of primary culture of villous trophoblastic cells. Connexin 43 and gap junctional intercellular communication point to the role of molecular exchanges through connexin channels preceding membrane fusion. Zona occludens-1, which can interact with connexin 43, is also directly involved in trophoblast fusion. The recently identified fusogenic membrane retroviral envelop glycoproteins syncytin 1 (encoded by the HERV-W gene) and syncytin 2 (encoded by the FRD gene) and their receptors are major factors involved in human placental development. We describe the increasing number of factors promoting or inhibiting trophoblast fusion and differentiation and emphasize the role of human chorionic gonadotropin (hCG) and its receptor. Indeed, in trisomy 21 the dynamic process leading to membrane fusion is impaired due to an abnormal hCG signaling. This abnormal trophoblast fusion and differentiation in trisomy 21-affected placenta is reversible in vitro. Trisomy 21 trophoblastic cell culture may therefore be useful to identify the possible large number of prerequisite factors involved in trophoblast fusion, the limiting step of trophoblast differentiation.
TÍTULO / TITLE:
- Impaired Plasticity at Specific Subset of Striatal Synapses in the Ts65Dn Mouse Model of Down Syndrome
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
-
AUTORES / AUTHORS:
- Di Filippo, M; Tozzi, A; Ghiglieri, V; Picconi, B; Costa, C; Cipriani, S; Tantucci, M; Belcastro, V; Calabresi, P
RESUMEN / SUMMARY:
- Background: Trisomy 21 or Down syndrome (DS) is the most frequent genetic cause of mental retardation. There is limited insight into the biological basis for the cognitive and motor deficits in DS. Because the striatum plays a key role in the regulation and learning of voluntary movements and in cognitive processes, our study was aimed at investigating striatal synaptic transmission and plasticity in a well-accepted genetic model of DS.
Methods: Electrophysiological recordings were performed in a corticostriatal slice preparation from trisomic (Ts65Dn) and wild-type mice. Synaptic properties and plasticity, long-term potentiation (LTP) and long-term depression (LTD), were investigated.
Results: The basal electrophysiological properties of striatal principal spiny neurons and cholinergic interneurons were spared in the Ts65Dn mouse model of DS. Striatal principal spiny neurons from Ts65Dn mice maintained their ability to undergo LTP and LTD. Conversely, LIP was lost in striatal cholinergic interneurons of Ts65Dn mice. The loss of LTP in striatal cholinergic interneurons of Ts65Dn mice was accompanied by a severe impairment of endogenous cholinergic signaling within the striatum.
Conclusions: The intrastriatal cholinergic system that was thought to be spared in DS is functionally altered in the Ts65Dn genetic model of DS. Altered cholinergic transmission might play a critical role in the pathophysiology of motor and cognitive deficits in DS, leading to an abnormal processing of neuronal inputs within the basal ganglia. Targeting striatal cholinergic transmission might represent a new therapeutic strategy in DS.
TÍTULO / TITLE:
- Memantine Normalizes Several Phenotypic Features in the Ts65Dn Mouse Model of Down Syndrome.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- J Alzheimers Dis. 2010 Apr 26.
AUTORES / AUTHORS:
- Rueda N; Llorens-Martin M; Florez J; Valdizan E; Banerjee P; Trejo JL; Martinez-Cue C
INSTITUCIÓN / INSTITUTION:
- Department of Physiology and Pharmacology, Faculty of Medicine, University of Cantabria, Santander, España.
RESUMEN / SUMMARY:
- Ts65Dn (TS) mice exhibit several phenotypic characteristics of human Down syndrome, including an increased brain expression of amyloid-beta protein precursor (AbetaPP) and cognitive disturbances. Aberrant N-methyl-D-aspartate (NMDA) receptor signaling has been suspected in TS mice, due to an impaired generation of hippocampal long-term potentiation (LTP). Memantine, an uncompetitive NMDA receptor antagonist approved for the treatment of moderate to severe Alzheimer’s disease, is known to normalize LTP and improve cognition in transgenic mice with high brain levels of AbetaPP and amyloid-beta protein. It has recently been demonstrated that acute injections of memantine rescue performance deficits of TS mice on a fear conditioning test. Here we show that oral treatment of aged TS mice with a clinically relevant dose of memantine (30 mg/kg/day for 9 weeks) improved spatial learning in the water maze task and slightly reduced brain AbetaPP levels. We also found that TS mice exhibited a significantly reduced granule cell count and vesicular glutamate transporter-1 (VGLUT1) labeling compared to disomic control mice. After memantine treatment, the levels of hippocampal VGLUT1 were significantly increased, reaching the levels observed in vehicle treated-control animals. Memantine did not significantly affect granule cell density. These data indicate that memantine may normalize several phenotypic abnormalities in TS mice, many of which - such as impaired cognition - are also associated with Down syndrome and Alzheimer’s disease.
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