Mutations of the cardiac β-mysin heavy-chain (β-MHC) gene cause hypertrophic cardiomyopathy (HCM). Recent genetype-phenotype correlation studies have shown that mutations carry prognostic significance, We studied five unrelated polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) method and the cycle sequencing of the PCR produts. A previously reported heterozygous mutation Arg719Gln (arginine→glutamine in codon 719) in exon 19 was found in one family. The proband is a 30-year-old female diagnosed at age of 25 years when she presented with showed moerate asymmetrical septal hypertrophy with left atrial enlargement. There was no obstruetion of the left ventricular outflow tract (LVOT) The patient also developed atrial fibrillation. The proband's mother and on of her ststers had similar clinical manifestations and both died sudenly at the age of 38 years. In addition. two silent nucleotide substitutions (ACT63ACC, TTT244TTC) in the cardiac β-MHC gene were klentified in the other four families.There synonyumous mutations did not cosegregate with the disease in the fanilies and they were also present in the 60 healthy and age-matched control subjects. Of the five families studied. we did not find any they were also present in the 60 healthy four families. The missense mutation Arg719Gln found in the Chines family is associated with a malignant phenotype f severe clinical symptoms and poor survival prognosis. This mutation also causes atrial enlargement and atrial fibrillation. Our study provides further evidence that the mutation, which alters the charge of the myosin heavy chain, is associated with a serious clinical outcome.