Assuntos
Displasia Arritmogênica Ventricular Direita/genética , Cardiomiopatia Dilatada/genética , Cardiomiopatia Hipertrófica Familiar/genética , Biologia Computacional/métodos , Mineração de Dados/métodos , Testes Genéticos/métodos , Variação Genética , Aprendizado de Máquina , Displasia Arritmogênica Ventricular Direita/classificação , Displasia Arritmogênica Ventricular Direita/diagnóstico , Cardiomiopatia Dilatada/classificação , Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Hipertrófica Familiar/classificação , Cardiomiopatia Hipertrófica Familiar/diagnóstico , Predisposição Genética para Doença , Hereditariedade , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Linhagem , Fenótipo , Valor Preditivo dos Testes , Prognóstico , Reprodutibilidade dos Testes , Medição de Risco , Fatores de RiscoRESUMO
About 10% of cases of hypertrophic cardiomyopathy (HCM) evolve into dilated cardiomyopathy (DCM) with unknown causes. We studied 11 unrelated patients (pts) with HCM who progressed to DCM (group A) and 11 who showed "typical" HCM (group B). Mutational analysis of the beta-myosin heavy chain (MYH7), myosin-binding protein C (MYBPC3), and cardiac troponin T (TNNT2) genes demonstrated eight mutations affecting MYH7 or MYBPC3 gene, five of which were new mutations. In group A-pts, the first new mutation occurred in the myosin head-rod junction and the second occurred in the light chain-binding site. The third new mutation leads to a MYBPC3 lacking titin and myosin binding sites. In group B, two pts with severe HCM carried two homozygous MYBPC3 mutations and one with moderate hypertrophy was a compound heterozygous for MYBPC3 gene. We identified five unreported mutations, potentially "malignant" defects as for the associated phenotypes, but no specific mutations of HCM/DCM.
