2. Academic Validation
  3. A new gene involved in X-linked mental retardation identified by analysis of an X;2 balanced translocation

A new gene involved in X-linked mental retardation identified by analysis of an X;2 balanced translocation

  • Nat Genet. 2000 Feb;24(2):167-70. doi: 10.1038/72829.
R Zemni 1,  T Bienvenu,  M C Vinet,  A Sefiani,  A Carrié,  P Billuart,  N McDonell,  P Couvert,  F Francis,  P Chafey,  F Fauchereau,  G Friocourt,  V des Portes,  A Cardona,  S Frints,  A Meindl,  O Brandau,  N Ronce,  C Moraine,  H van Bokhoven,  H H Ropers,  R Sudbrak,  A Kahn,  J P Fryns,  C Beldjord,  J Chelly
Affiliations

Affiliation

  • 1 INSERM Unité 129 - ICGM, CHU Cochin, Paris, France.
PMID: 10655063 DOI: 10.1038/72829
Abstract

X-linked forms of mental retardation (MR) affect approximately 1 in 600 males and are likely to be highly heterogeneous. They can be categorized into syndromic (MRXS) and nonspecific (MRX) forms. In MRX forms, affected patients have no distinctive clinical or biochemical features. At least five MRX genes have been identified by positional cloning, but each accounts for only 0.5%-1.0% of MRX cases. Here we show that the gene TM4SF2 at Xp11.4 is inactivated by the X breakpoint of an X;2 balanced translocation in a patient with MR. Further investigation led to identification of TM4SF2 mutations in 2 of 33 other MRX families. RNA in situ hybridization showed that TM4SF2 is highly expressed in the central nervous system, including the cerebral cortex and hippocampus. TM4SF2 encodes a member of the tetraspanin family of proteins, which are known to contribute in molecular complexes including beta-1 integrins. We speculate that through this interaction, TM4SF2 might have a role in the control of neurite outgrowth.

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