[Update on the genetics of X-linked mental retardation].
Mutations in X-linked genes are likely to account for the observation that more males than females are affected with mental retardation. Causative mutations have been identified in both syndromic XLMR and in the genetically heterogeneous non-syndromic forms of XLMR, without a clear clinical phenotype other than cognitive deficit. Progress in genome analysis and the establishment of large collaborations between clinical and molecular research teams, especially the European XLMR consortium, have led to the identification of 20 non-syndromic XLMR genes and 25 syndromic XLMR genes. Given the extensive heterogeneity of non syndromic XLMR, different strategies are used for the identification of new genes: linkage analysis, studies of balanced chromosomal rearrangements (X-autosome translocations, microdeletions) and candidate genes strategies by mutation screening in regions of the X chromosome known to be involved in neuronal development and function. Delineating the monogenic causes of XLMR and their molecular and cellular consequences will provide insight into the mechanisms that are required for normal development of cognitive function in humans. Non syndromic XLMR proteins include 5 distinct classes: transmembrane receptors, small GTPases effectors or regulators, enzymes and translational regulators.
Bahi-Buisson
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Département de Pédiatrie, Service de Neuropédiatrie et Maladies Métaboliques, Hôpital Necker, and Université René Descartes, Paris, France. nadia.bahi-buisson@nck.ap-hop-paris.fr
Chelly
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J
des Portes
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V
D041321:Chromosomes, Human, X; D006801:Humans; D008607:Intellectual Disability / Q000145:classification / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D015995:Prevalence; D025064:Sex Chromosome Disorders / Q000235:genetics*; D013569:Synapses / Q000473:pathology; D014158:Transcription, Genetic