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: 24181.0, MPI für molekulare Genetik / Department of Human Molecular Genetics
FACL4, encoding fatty acid-CoA ligase 4, is mutated in
nonspecific X-linked mental retardation
Authors:Meloni, Ilaria; Muscettola, Maddalena; Raynaud, Martine; Longo, Ilaria; Bruttini, Mirella; Moizard, Marie-Pierre; Gomot, Marie; Chelly, Jamel; des Portes, Vincent; Fryns, Jean-Pierre; Ropers, Hans Hilger; Magi, Barbara; Bellan, Cristina; Volpi, Nila; Yntema, Helger G.; Lewis, Sarah E.; Schaffer, Jean E.; Renieri, Alessandra
Language:English
Date of Publication (YYYY-MM-DD):2002-03
Title of Journal:Nature Genetics
Volume:30
Issue / Number:4
Start Page:436
End Page:440
Review Status:not specified
Audience:Experts Only
Abstract / Description:X-linked mental retardation (XLMR) is an inherited condition that causes failure to develop cognitive abilities, owing to mutations in a gene on the X chromosome. The latest XLMR update lists up to 136 conditions leading to 'syndromic', or 'specific', mental retardation (MRXS) and 66 entries leading to 'nonspecific' mental retardation (MRX)1. For 9 of the 66 MRX entries, the causative gene has been identified1. Our recent discovery of the contiguous gene deletion syndrome ATS-MR (previously known as Alport syndrome, mental retardation, midface hypoplasia, elliptocytosis, OMIM #300194), characterized by Alport syndrome (ATS) and mental retardation (MR), indicated Xq22.3 as a region containing one mental retardation gene2, 3. Comparing the extent of deletion between individuals with ATS-MR and individuals with ATS alone allowed us to define a critical region for mental retardation of approximately 380 kb, containing four genes4-6. Here we report the identification of two point mutations, one missense and one splice-site change, in the gene FACL4 in two families with nonspecific mental retardation. Analysis of enzymatic activity in lymphoblastoid cell lines from affected individuals of both families revealed low levels compared with normal cells, indicating that both mutations are null mutations. All carrier females with either point mutations or genomic deletions in FACL4 showed a completely skewed X-inactivation, suggesting that the gene influences survival advantage. FACL4 is the first gene shown to be involved in nonspecific mental retardation and fatty-acid metabolism.
External Publication Status:published
Document Type:Article
Communicated by:Hans-Hilger Ropers
Affiliations:MPI für molekulare Genetik
External Affiliations:Medical Genetics, Department of Molecular Biology, University of Siena, Italy
Service de Génétique, Inserm U316, Tours cédex, France
Inserm U129-ICGM, CHU Cochin, Paris, France
Genetics Department, University of Leuven, Belgium
Biochemistry, Department of Molecular of Biology, University of Siena, Italy
Department of Pathology, University of Siena, Italy
Department of Biomedical Sciences, University of Siena, Italy
Department of Human Genetics, Nijmegen, The Netherlands
Departments of Internal Medicine, Molecular Biology & Pharmacology, Washington University, St. Louis, Missouri, USA
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.