Nature Genetics
24, 167 - 170 (2000)
doi:10.1038/72829
A new gene involved in X-linked mental retardation identified by analysis
of an X;2 balanced translocationRamzi Zemni1, Thierry Bienvenu1, Marie C. Vinet1, Aziz Sefiani2, Alain Carrié1, Pierre Billuart1, Nathalie McDonell1, Philippe Couvert1, Fiona Francis1, Philippe Chafey1, Fabien Fauchereau1, Gaelle Friocourt1, Vincent des Portes1, Anna Cardona3, Suzanna Frints4, Alfonse Meindl5, Oliver Brandau5, Nathalie Ronce6, Claude Moraine6, Han van Bokhoven7, Hans H. Ropers8, Ralf Sudbrak9, Axel Kahn1, Jean P Fryns4, Cherif Beldjord1
& Jamel Chelly11
INSERM Unité 129 − ICGM, CHU Cochin,
Paris, France. 2
Institut National d'Hygiène, Rabat
, Maroc. 3
Laboratoire de technologie cellulaire, Institut Pasteur
, Paris, France. 4
Center for Human Genetics, Clinical Genetics University,
UZ Gasthuisberg, Leuven, Belgium. 5
Ludwig-Maximilians-Universität München, Abteilung
Medizinische Genetik, München, Germany. 6
Centre Hospitalier de Tours, Service de Génétique,
Hopital Bretonneau, Tours Cedex, France. 7
University Hospital Nijmegen, 417 Department
of Human Genetics, >Nijmegen, The Netherlands.
8
Max-Planck-Institute for Molecular Genetics,
Berlin-Dahlem, Germany. 9
Max-Planck-Institute for Molecular Genetics, Abt. Lehrach
, Berlin-Dahlem, Germany.
Correspondence should be addressed to Jamel Chelly chelly@infobiogen.fr.X-linked forms of mental retardation (MR) affect approximately 1 in 600
males and are likely to be highly heterogeneous1,
2,
3. 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 cases4,
5. 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  -1 integrins6,
7,
8. We speculate that through this interaction, TM4SF2 might
have a role in the control of neurite outgrowth.
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