title: The ARX mutations: a frequent cause of X-linked mental retardation.
abstract: The ARX gene mutations have been demonstrated to cause different forms of mental retardation (MR). Beside FMR1, in families with X-linked mental retardation (XLMR), the ARX dysfunction was demonstrated to be among the most frequent causes of this heterogeneous group of disorders. Nevertheless, in sporadic cases of MR, ARX mutations are extremely rare. In order to evaluate the frequency of ARX mutation in XLMR, we performed mutational analysis of ARX in 165 mentally retarded probands negative for FRAXA and belonging to families in which the condition segregates as an X-linked condition. The same recurrent mutation, an in frame 24 bp insertion (c.428-451 dup (24 bp)), was identified in five patients. In one family, the mother of two affected boys was found not to carry the mutation detected in her sons. These data suggest the presence of germline mosaicism for the mutation in the mother. Our results confirm the significant contribution of ARX mutations in the etiology of MR, especially in this group of patients selected for XLMR (3%). These data, together with those reported in the literature, imply that screening for c.428-451 dup (24 bp) mutation should be recommended in all patients with suspected XLMR.
authors.affiliation: Department of Medical Genetics, Institute of Mother and Child, Kasprzaka 17a, Warsaw, Poland. mnawara@imid.med.pl
authors.forename: Magdalena
authors.initials: M
authors.lastname: Nawara
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Szczaluba
authors.forename: Karine
authors.initials: K
authors.lastname: Poirier
authors.forename: Krystyna
authors.initials: K
authors.lastname: Chrzanowska
authors.forename: Jacek
authors.initials: J
authors.lastname: Pilch
authors.forename: Jerzy
authors.initials: J
authors.lastname: Bal
authors.forename: Jamel
authors.initials: J
authors.lastname: Chelly
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Mazurczak
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D005820:Genetic Testing; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D038901:X-Linked Intellectual Disability / Q000175:diagnosis / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C469264:ARX protein, human; D018398:Homeodomain Proteins; D014157:Transcription Factors