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          Institute: MPI für molekulare Genetik     Collection: Department of Human Molecular Genetics     Display Documents



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ID: 307641.0, MPI für molekulare Genetik / Department of Human Molecular Genetics
Disruptions of the novel KIAA1202 gene are associated with X-linked mental retardation
Authors:Hagens, Olivier; Dubos, Aline; Abidi, Fatima; Barbi, Gotthold; Van Zutven, Laura; Hoeltzenbein, Maria; Tommerup, Niels; Moraine, Claude; Fryns, Jean-Pierre; Chelly, Jamel; van Bokhoven, Hans; Gécz, Jozef; Dollfus, Hélène; Ropers, Hans-Hilger; Schwartz, Charles E.; de Cassia Stocco dos Santos, Rita; Kalscheuer, Vera M.; Hanauer, André
Language:English
Date of Publication (YYYY-MM-DD):2006-01-01
Title of Journal:Human Genetics
Journal Abbrev.:Hum. Gen.
Volume:118
Issue / Number:5
Start Page:578
End Page:590
Copyright:© Springer. Part of Springer Science+Business Media
Review Status:not specified
Audience:Experts Only
Abstract / Description:The extensive heterogeneity underlying the genetic component of mental retardation (MR) is the main cause for our limited understanding of the aetiology of this highly prevalent condition. Hence we set out to identify genes involved in MR. We investigated the breakpoints of two balanced X;autosome translocations in two unrelated female patients with mild/moderate MR and found that the Xp11.2 breakpoints disrupt the novel human KIAA1202 (hKIAA1202) gene in both cases. We also identified a missense exchange in this gene, segregating with the Stocco dos Santos XLMR syndrome in a large four-generation pedigree but absent in >1,000 control X-chromosomes. Among other phenotypic characteristics, the affected males in this family present with severe MR, delayed or no speech, seizures and hyperactivity. Molecular studies of hKIAA1202 determined its genomic organisation, its expression throughout the brain and the regulation of expression of its mouse homologue during development. Transient expression of the wild-type KIAA1202 protein in HeLa cells showed partial colocalisation with the F-actin based cytoskeleton. On the basis of its domain structure, we argue that hKIAA1202 is a new member of the APX/Shroom protein family. Members of this family contain a PDZ and two ASD domains of unknown function and have been shown to localise at the cytoskeleton, and play a role in neurulation, cellular architecture, actin remodelling and ion channel function. Our results suggest that hKIAA1202 may be important in cognitive function and/or development.
Comment of the Author/Creator:Email: kalscheu@molgen.mpg.de
Supplementary material is available for this article at http://dx.doi.org/10.1007/10.1007/s00439-005-0072-2 and is accessible for authorized users.
External Publication Status:published
Document Type:Article
Communicated by:Hans-Hilger Ropers
Affiliations:MPI für molekulare Genetik
External Affiliations:1.Department of Molecular Pathology, Institut de Génétique et de Biologie Moléculaire et Cellulaire (CNRS/INSERM/ULP), Illkirch, France;
2.J. C. Self Research Institute, Greenwood Genetic Center, Greenwood, USA;
3.Department of Human Genetics, University of Ulm, Ulm, Germany;
4.Department of Medical Biochemistry and Genetics, Wilhelm Johannsen Centre for Functional Genome Research, Copenhagen, Denmark;
5.Services de Génétique (INSERM), Tours, France;
6.Centre for Human Genetics, University Hospital Leuven, Leuven, Belgium;
7.Institut Cochin de Génétique Moléculaire, Centre National de la Recherche Scientifique (INSERM), Paris, France;
8.Department of Human Genetics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands;
9.Department of Genetic Medicine, Women’s and Children’s Hospital and Department of Pediatrics, University of Adelaide, Adelaide, Australia;
10.Service de Génétique Médicale, Hopitaux Universitaires de Strasbourg, Strasbourg, France;
11.Laboratório de Genética, Instituto Butantan, Universidade de Taubaté, São Paulo, Brazil.
Identifiers:ISSN:0340-6717
DOI:10.1007/s00439-005-0072-2
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