RESUMO
Barth syndrome (BTHS) is an X-linked recessive disease caused by mutations in tafazzin gene (TAZ) which lead to cardiolipin deficiency and mitochondrial dysfunction. Male patients have variable clinical findings, including cardiomyopathy, skeletal myopathy, prepubertal short stature, neutropenia and 3-methylglutaconic aciduria. Female carriers are usually asymptomatic. We report a novel TAZ gene mutation in male and female siblings with left ventricular noncompaction and hypotonia. Additionally, the brother presented an intermittent neutropenia and increased urinary levels of 3-methylglutaconic and 3-methylglutaric acid. The molecular genetic testing showed that both siblings carry the mutation: c.253insC, p.(Arg85Profs*54) in exon 3 of the TAZ gene. This article presents the first case of BTHS in a heterozygous female patient with normal karyotype.
Assuntos
Síndrome de Barth/genética , Análise Mutacional de DNA , Fatores de Transcrição/genética , Aciltransferases , Adolescente , Síndrome de Barth/diagnóstico , Bulgária , Cardiolipinas/metabolismo , Criança , Anormalidades Craniofaciais/diagnóstico , Anormalidades Craniofaciais/genética , Feminino , Triagem de Portadores Genéticos , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/genética , Humanos , Cariotipagem , Masculino , Doenças Mitocondriais/diagnóstico , Doenças Mitocondriais/genética , Hipotonia Muscular/diagnóstico , Hipotonia Muscular/genética , Inativação do Cromossomo X/genéticaRESUMO
Many studies have supported a genetic aetiology for autism. Neuroligins are postsynaptically located cell-adhesion molecules. Mutations in two X-linked neuroligin genes, NLGN3 and NLGN4, have been implicated in pathogenesis of autism. In order to confirm these causative mutations in our autistic population and to determine their frequency we screened 20 individuals affected with autism. We identified one patient with a point mutation in NLGN4 gene that substituted a Met for Thr 787 - c.2360C > T, p.(Thr787Met) and three patients with identical polymorphisms in the same gene: c.933C > T, p.(Thr311Thr) in combination with c.[1777C > T+1779C > G, p.(Leu593Leu)]. All patients tested for NLGN3 mutations were negative. These results indicate that mutations in these genes are responsible for at most a small fraction of autism cases.