Subject(s)
Arrhythmogenic Right Ventricular Dysplasia/genetics , Cardiomyopathy, Dilated/genetics , Cardiomyopathy, Hypertrophic, Familial/genetics , Computational Biology/methods , Data Mining/methods , Genetic Testing/methods , Genetic Variation , Machine Learning , Arrhythmogenic Right Ventricular Dysplasia/classification , Arrhythmogenic Right Ventricular Dysplasia/diagnosis , Cardiomyopathy, Dilated/classification , Cardiomyopathy, Dilated/diagnosis , Cardiomyopathy, Hypertrophic, Familial/classification , Cardiomyopathy, Hypertrophic, Familial/diagnosis , Genetic Predisposition to Disease , Heredity , High-Throughput Nucleotide Sequencing , Humans , Pedigree , Phenotype , Predictive Value of Tests , Prognosis , Reproducibility of Results , Risk Assessment , Risk FactorsABSTRACT
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.
