title: A new gene involved in X-linked mental retardation identified by analysis of an X;2 balanced translocation.
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.
authors.affiliation: INSERM Unité 129 - ICGM, CHU Cochin, Paris, France.
authors.forename: R
authors.initials: R
authors.lastname: Zemni
authors.forename: T
authors.initials: T
authors.lastname: Bienvenu
authors.forename: M C
authors.initials: MC
authors.lastname: Vinet
authors.forename: A
authors.initials: A
authors.lastname: Sefiani
authors.forename: A
authors.initials: A
authors.lastname: Carrié
authors.forename: P
authors.initials: P
authors.lastname: Billuart
authors.forename: N
authors.initials: N
authors.lastname: McDonell
authors.forename: P
authors.initials: P
authors.lastname: Couvert
authors.forename: F
authors.initials: F
authors.lastname: Francis
authors.forename: P
authors.initials: P
authors.lastname: Chafey
authors.forename: F
authors.initials: F
authors.lastname: Fauchereau
authors.forename: G
authors.initials: G
authors.lastname: Friocourt
authors.forename: V
authors.initials: V
authors.lastname: des Portes
authors.forename: A
authors.initials: A
authors.lastname: Cardona
authors.forename: S
authors.initials: S
authors.lastname: Frints
authors.forename: A
authors.initials: A
authors.lastname: Meindl
authors.forename: O
authors.initials: O
authors.lastname: Brandau
authors.forename: N
authors.initials: N
authors.lastname: Ronce
authors.forename: C
authors.initials: C
authors.lastname: Moraine
authors.forename: H
authors.initials: H
authors.lastname: van Bokhoven
authors.forename: H H
authors.initials: HH
authors.lastname: Ropers
authors.forename: R
authors.initials: R
authors.lastname: Sudbrak
authors.forename: A
authors.initials: A
authors.lastname: Kahn
authors.forename: J P
authors.initials: JP
authors.lastname: Fryns
authors.forename: C
authors.initials: C
authors.lastname: Beldjord
authors.forename: J
authors.initials: J
authors.lastname: Chelly
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D001921:Brain / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D002648:Child; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2; D005091:Exons; D005260:Female; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D007621:Karyotyping; D008297:Male; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D059470:Tetraspanins; D014178:Translocation, Genetic; D014960:X Chromosome
chemical_list: D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C404405:TSPAN7 protein, human; D059470:Tetraspanins