Screening of ARX in mental retardation families : consequences for the strategy of molecular diagnosis

• Published in: Neurogenetics Vol. 7; no. 1; pp. 39 - 46
• Main Authors: POIRIER, K, LACOMBE, D, CHELLY, J, BIENVENU, T, GILBERT-DUSSARDIER, B, RAYNAUD, M, DESPORTES, V, DE BROUWER, A. P. M, MORAINE, C, FRYNS, J. P, ROPERS, H. H, BEIDJORD, C
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01-03-2006; Springer Nature B.V; Springer Verlag
• Subjects: Adult and adolescent clinical studies; Amino Acid Sequence; Animals; Biological and medical sciences; DNA Mutational Analysis; Female; General aspects. Genetic counseling; Genetic Testing; Genetics; Homeodomain Proteins - genetics; Humans; Intellectual deficiency; Intellectual disabilities; Life Sciences; Male; Medical diagnosis; Medical genetics; Medical sciences; Mental Retardation, X-Linked - diagnosis; Mental Retardation, X-Linked - genetics; Molecular Diagnostic Techniques; Molecular Sequence Data; Mutation; Pedigree; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Syndrome; Transcription Factors - genetics; ARX mutations; Nervous system diseases; PRTS; Family study; Developmental disorder; Medical screening; Mental retardation; ISSX; Screening; Intellectual deficiency; Family environment; Genetics; Strategy; X-Chromosome; Diagnosis; Mutation
• ISSN: 1364-6745; 1364-6753
• DOI: 10.1007/s10048-005-0014-0

Mutations in the human ARX gene have been shown to cause nonsyndromic X-linked mental retardation (MRX) as well as syndromic forms such as X-linked lissencephaly with abnormal genitalia (XLAG), Partington syndrome and X-linked infantile spasm. The most common causative mutation, a duplication of 24 bp, was found in families with a variety of phenotypes, but not in the more severe XLAG phenotypes. The aim of the study was to access the frequency of ARX mutations in families with established or putative X-linked mental retardation (XLMR) collected by the European XLMR Consortium. We screened the entire coding region of ARX for mutations in 197 novel XLMR families by denaturing high-performance liquid chromatography, and we identified eight mutations (six c.428_451dup24, one insertion and one novel missense mutation p.P38S). To better define the prevalence of ARX mutations, we included previously reported results of 157 XLMR families. Together, these data showed the relatively high rate (9.5%) of ARX mutations in X-linked MR families and an expectedly low rate in families with affected brother pairs (2.2%). This study confirms that the frequency of ARX mutations is high in XLMR, and the analysis of ARX in MRX should not be limited to duplication.