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|dc.contributor.author||Van Esch, H.||en|
|dc.identifier.citation||American Journal of Human Genetics, 2005; 77(3):442-453||en|
|dc.description.abstract||Loss-of-function mutations of the MECP2 gene at Xq28 are associated with Rett syndrome in females and with syndromic and nonsyndromic forms of mental retardation (MR) in males. By array comparative genomic hybridization (array-CGH), we identified a small duplication at Xq28 in a large family with a severe form of MR associated with progressive spasticity. Screening by real-time quantitation of 17 additional patients with MR who have similar phenotypes revealed three more duplications. The duplications in the four patients vary in size from 0.4 to 0.8 Mb and harbor several genes, which, for each duplication, include the MR-related L1CAM and MECP2 genes. The proximal breakpoints are located within a 250-kb region centromeric of L1CAM, whereas the distal breakpoints are located in a 300-kb interval telomeric of MECP2. The precise size and location of each duplication is different in the four patients. The duplications segregate with the disease in the families, and asymptomatic carrier females show complete skewing of X inactivation. Comparison of the clinical features in these patients and in a previously reported patient enables refinement of the genotype-phenotype correlation and strongly suggests that increased dosage of MECP2 results in the MR phenotype. Our findings demonstrate that, in humans, not only impaired or abolished gene function but also increased MeCP2 dosage causes a distinct phenotype. Moreover, duplication of the MECP2 region occurs frequently in male patients with a severe form of MR, which justifies quantitative screening of MECP2 in this group of patients.||en|
|dc.description.statementofresponsibility||Hilde Van Esch, Marijke Bauters, Jaakko Ignatius, Mieke Jansen, Martine Raynaud, Karen Hollanders, Dorien Lugtenberg, Thierry Bienvenu, Lars Riff Jensen, Jozef Gécz, Claude Moraine, Peter Marynen, Jean-Pierre Fryns and Guy Froyen||en|
|dc.publisher||Univ Chicago Press||en|
|dc.rights||© 2005 The American Society of Human Genetics Published by Elsevier Inc.||en|
|dc.subject||Chromosomes, Human, X; Humans; Genetic Predisposition to Disease; DNA Primers; Nucleic Acid Hybridization; Pedigree; Gene Duplication; Gene Dosage; Male; Methyl-CpG-Binding Protein 2; Intellectual Disability||en|
|dc.title||Duplication of the MECP2 region is a frequent cause of severe mental retardation and progressive neurological symptoms in males||en|
|dc.identifier.orcid||Gecz, J. [0000-0002-7884-6861]||en|
|Appears in Collections:||Paediatrics publications|
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