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
Citrin deficiency is an autosomal recessive disorder caused by mutations in the SLC25A13 gene and has three phenotypes: neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) in newborns, failure to thrive and dyslipidemia caused by citrin deficiency (FTTDCD) in older children, and recurrent hyperammonemia with neuropsychiatric symptoms in citrullinemia type II (CTLN2) in adults. NICCD presents in the first few weeks of life with cholestatic hepatitis syndrome, multiple aminoacidemia and hypergalactosemia. To date almost all reported patients were from East Asia and only few cases from Caucasian origin have been described. We report the first Bulgarian case of NICCD. Mutation screening of the SLC25A13 gene revealed the compound heterozygous mutations c.1081C>T (p.R361*) and c.74C>A (p. A25E) which confirmed the diagnosis of NICCD. The nonsense mutation c.1081C>T (p.R361*) is novel.
Assuntos
Proteínas de Ligação ao Cálcio/deficiência , Citrulinemia/genética , Análise Mutacional de DNA , Proteínas de Transporte da Membrana Mitocondrial/genética , Transportadores de Ânions Orgânicos/deficiência , Arginina/sangue , Bulgária , Citrulina/sangue , Citrulinemia/sangue , Citrulinemia/diagnóstico , Citrulinemia/dietoterapia , Feminino , Seguimentos , Galactose/administração & dosagem , Triagem de Portadores Genéticos , Humanos , Recém-Nascido , Masculino , Metionina/sangue , Mutação de Sentido Incorreto/genética , Fenótipo , Gravidez , População Branca/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.
