Home News About Us Contact Contributors Disclaimer Privacy Policy Help FAQ

Home
Search
Quick Search
Advanced
Fulltext
Browse
Collections
Persons
My eDoc
Session History
Login
Name:
Password:
Documentation
Help
Support Wiki
Direct access to
document ID:


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



  history
ID: 333783.0, MPI für molekulare Genetik / Department of Human Molecular Genetics
Mutation frequencies of X-linked mental retardation genes in families from the EuroMRX consortium
Authors:de Brouwer, Arjan P.M.; Yntema, Helger G.; Kleefstra, Tjitske; Lugtenberg, Dorien; Oudakker, Astrid R.; de Vries, Bert B. A.; van Bokhoven, Hans; van Esch, Hilde; Frints, Suzanne G. M.; Froyen, Guy; Fryns, Jean-Pierre; Raynaud, Martine; Moizard, Marie-Pierre; Ronce, Nathalie; Bensalem, Anissa; Moraine, Claude; Poirier, Karine; Castelnau, Laetitia; Saillour, Yoann; Bienvenu, Thierry; Beldjord, Chérif; des Portes, Vincent; Chelly, Jamel; Turner, Gillian; Fullston, Tod; Gecz, Jozef; Kuss, Andreas W.; Tzschach, Andreas; Jensen, Lars Riff; Lenzner, Steffen; Kalscheuer, Vera M.; Ropers, Hans-Hilger; Hamel, Ben C.J.
Language:English
Research Context:5th European Union Framework, ZonMw, and ANR; Grant Number: QLG3-CT-2002-01810, 2100.0041, ANR-05-NEU-40-01
Date of Publication (YYYY-MM-DD):2007-01-12
Title of Journal:Human Mutation
Journal Abbrev.:Hum mut
Volume:28
Issue / Number:2
Start Page:207
End Page:208
Copyright:© 2007 Wiley-Liss, Inc.
Review Status:not specified
Audience:Experts Only
Abstract / Description:The EuroMRX family cohort consists of about 400 families with non-syndromic and 200 families with syndromic X-linked mental retardation (XLMR). After exclusion of Fragile X (Fra X) syndrome, probands from these families were tested for mutations in the coding sequence of 90 known and candidate XLMR genes. In total, 73 causative mutations were identified in 21 genes. For 42% of the families with obligate female carriers, the mental retardation phenotype could be explained by a mutation. There was no difference between families with (lod score >2) or without (lod score <2) significant linkage to the X chromosome. For families with two to five affected brothers (brother pair=BP families) only 17% of the MR could be explained. This is significantly lower (P=0.0067) than in families with obligate carrier females and indicates that the MR in about 40% (17/42) of the BP families is due to a single genetic defect on the X chromosome. The mutation frequency of XLMR genes in BP families is lower than can be expected on basis of the male to female ratio of patients with MR or observed recurrence risks. This might be explained by genetic risk factors on the X chromosome, resulting in a more complex etiology in a substantial portion of XLMR patients. The EuroMRX effort is the first attempt to unravel the molecular basis of cognitive dysfunction by large-scale approaches in a large patient cohort. Our results show that it is now possible to identify 42% of the genetic defects in non-syndromic and syndromic XLMR families with obligate female carriers
Free Keywords:mental retardation • MRX • MRXS • X chromosome • brother pair families • mutation frequency
Comment of the Author/Creator:email: Arjan P.M. de Brouwer (A.debrouwer@antrg.umcn.nl)
Correspondence to Arjan P.M. de Brouwer, Department of Human Genetics, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands
Communicated by Andreas Gal
External Publication Status:published
Document Type:Article
Communicated by:Hans-Hilger Ropers
Affiliations:MPI für molekulare Genetik
External Affiliations:1.Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands;
2.Centre for Human Genetics, University Hospital Leuven, Leuven, Belgium;
3.Unité de Génétique, CHU Bretonneau, Tours, France;
4.Institut Cochin (IC), Département de Génétique et Pathologie Moléculaire GDPM, Equipe de Génétique et Physiopathologie du Retard Mental GPRM, Paris, France;
5.NSW GOLD Service, Hunter Genetics, University of Newcastle, Waratah, Australia;
6.Department of Genetic Medicine, Women's and Children's Hospital, and Departments of Paediatrics and Molecular Biosciences, University of Adelaide, Adelaide, Australia.
Identifiers:ISSN:1098-1004
DOI:10.1002/humu.9482
Full Text:
Sorry, no privileges
The scope and number of records on eDoc is subject to the collection policies defined by each institute - see "info" button in the collection browse view.