[X-linked mental retardation].
X-linked mental retardation (XLMR) affects 1.8 per thousand male births and is usually categorized as "syndromic" (MRXS) or "non-specific" (MRX) forms according to the presence or absence of specific signs in addition to the MR. Up to 60 genes have been implicated in XLMR and certain mutations can alternatively lead to MRXS or MRX. Indeed the extreme phenotypic and allelic heterogeneity of XLMR makes the classification of most genes difficult. Therefore, following identification of new genes, accurate retrospective clinical evaluation of patients and their families is necessary to aid the molecular diagnosis and the classification of this heterogeneous group of disorders. Analyses of the protein products corresponding to XLMR genes show a great diversity of cellular pathways involved in MR. Common mechanisms are beginning to emerge : a first group of proteins belongs to the Rho and Rab GTPase signaling pathways involved in neuronal differentiation and synaptic plasticity and a second group is related to the regulation of gene expression. In this review, we illustrate the complexity of XLMR conditions and present recent data about the FMR1, ARX and Oligophrenin 1 genes.
Billuart
Pierre
P
Institut Cochin, GDPM, 24, rue du Faubourg-St-Jacques, 75014 Paris, France. billuart@cochin.inserm.fr
Chelly
Jamel
J
Gilgenkrantz
Simone
S
D002353:Carrier State; D002454:Cell Differentiation / Q000235:genetics; D041321:Chromosomes, Human, X / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics / Q000502:physiology; D005600:Fragile X Syndrome / Q000235:genetics; D020690:GTPase-Activating Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology; D006801:Humans; D008297:Male; D038901:X-Linked Intellectual Disability / Q000145:classification / Q000175:diagnosis / Q000235:genetics*; D008957:Models, Genetic; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D010641:Phenotype; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology
D003598:Cytoskeletal Proteins; D051860:Fragile X Messenger Ribonucleoprotein 1; D020690:GTPase-Activating Proteins; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; C469264:ARX protein, human; C497683:FMR1 protein, human; C111952:OPHN1 protein, human