title: Mutational screening of ARX gene in Brazilian males with mental retardation of unknown etiology.
abstract: ARX gene mutations have been known as important causes of developmental and neurological disorders and are responsible for a large spectrum of abnormal phenotypes, includeing syndromic as well as nonsyndromic forms of mental retardation. We have screened the entire coding and flanking intronic sequences of ARX gene in 143 mentally impaired males in order to investigate the contribution of ARX mutations to mental retardation in the population of Rio de Janeiro, Brazil. Three sequence variants were identified: one patient had the most recurrent mutation already observed in ARX gene, the c.428_451dup(24 bp), two patients presented the c.1347C>T (p.G449G) in exon 4, and one patient had the intronic variant c.1074-3T>C. Although two of these alterations were considered polymorphisms, the known pathogenic variant c.428_451dup(24 bp) was found at a high rate (4.8%) among X-linked mental retardation (XLMR) families. Our results, the first in Latin America, reinforce the idea that ARX mutations are relevant to mental retardation and are indicative that molecular screening of exon 2 should be considered in males with mental retardation of unknown etiology, associated or not with neurological manifestations, especially in familial cases.
authors.affiliation: Serviço de Genética Humana, Departamento de Biologia Celular e Genética, Instituto de Biologia Roberto Alcântara Gomes, Universidade do Estado do Rio de Janeiro, Rua São Francisco Xavier 524, PHLC sala 500, Maracanã, Rio de Janeiro, 20550-013, Brazil.
authors.forename: Raquel
authors.initials: R
authors.lastname: de Souza Gestinari-Duarte
authors.affiliation: Serviço de Genética Humana, Departamento de Biologia Celular e Genética, Instituto de Biologia Roberto Alcântara Gomes, Universidade do Estado do Rio de Janeiro, Rua São Francisco Xavier 524, PHLC sala 500, Maracanã, Rio de Janeiro, 20550-013, Brazil.
authors.forename: Cíntia Barros
authors.initials: CB
authors.lastname: Santos-Rebouças
authors.affiliation: Serviço de Genética Humana, Departamento de Biologia Celular e Genética, Instituto de Biologia Roberto Alcântara Gomes, Universidade do Estado do Rio de Janeiro, Rua São Francisco Xavier 524, PHLC sala 500, Maracanã, Rio de Janeiro, 20550-013, Brazil. pimentel@uerj.br.
authors.forename: Márcia Mattos Gonçalves
authors.initials: MMG
authors.lastname: Pimentel
mesh_terms: D001938:Brazil; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005820:Genetic Testing; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008607:Intellectual Disability / Q000209:etiology / Q000235:genetics*; D008297:Male; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C469264:ARX protein, human; D018398:Homeodomain Proteins; D014157:Transcription Factors