THE ELECTROCARDIOGRAM IS A MORE SENSITIVE INDICATOR THAN ECHOCARDIOGRAPHY OF HYPERTROPHIC CARDIOMYOPATHY IN FAMILIES WITH A MUTATION IN THEMYH7 GENE

Background-Mutations in the cardiac beta myosin heavy chain gene causi ng hypertrophic cardiomyopathy have been identified, and to assist bot h diagnosis and prediction of outcome attempts have been made to corre late phenotype and genotype. Two new mutations in codon 403 of the gen e in three unrelated families are described and attention drawn to var iable or even absent phenotypic expression in different family members . Methods and Results-The polymerase chain reaction and heteroduplex a nalysis on Mutation Detection Enhancement gels were used to search for mutations in the globular head of the beta myosin heavy chain gene in families with hypertrophic cardiomyopathy. Two mutations were found i n exon 13 (codon 403) of the gene. In two unrelated Polish families th e mutation resulted in the conversion of arginine to tryptophan (CGG - -> TGG). A second mutation, found in a British family, converted the s ame arginine to leucine (CGG --> CTG). These mutations were detected i n family members who had electrocardiographic and echocardiographic fe atures typical of hypertrophic cardiomyopathy; however, they were also detected in 7 other adult relatives with an abnormal electrocardiogra m but a normal echocardiogram. Two unrelated adult relatives had compl etely normal clinical findings but carried the gene mutation. Conclusi ons-Identification of a specific mutation gives no guide to the clinic al phenotype. There is considerable variability in the phenotypic expr ession of hypertrophic cardiomyopathy. Mutations were detected in adul ts previously regarded as normal or in whom the diagnosis was question able. The fact that the clinical significance of the mutation in these people is still unknown emphasises the dilemma facing screening progr ammes. Isolated, unexplained electrocardiographic abnormalities in fir st degree relatives in a family with a definitive diagnosis of hypertr ophic cardiomyopathy should be regarded as evidence of a carrier state .