GENOTYPE-PHENOTYPE CORRELATIONS IN FAMILIAL HYPERTROPHIC CARDIOMYOPATHY - A COMPARISON BETWEEN MUTATIONS IN THE CARDIAC PROTEIN-C AND THE BETA-MYOSIN HEAVY-CHAIN GENES

Background. The gene involved in familial hypertrophic cardiomyopathy on chromosome 11 was recently identified as the cardiac myosin binding protein-C (MyBP-C) gene. The phenotype of two families associated wit h mutation in this gene is described here and compared to that of five families with mutations in the beta-myosin heavy chain gene. Methods and results. In adults (n=33) bearing a splice acceptor site mutation in the MyBP-C gene, penetrance of familial hypertrophic cardiomyopathy was incomplete (69%) and ventricular hypertrophy mild. Among 37 clini cal, electrocardiographic and echocardiographic parameters analysed, t he only difference with the beta-MHC group (n=35) was a shorter accele ration time of systolic How in the pulmonary artery (P<0.05). Sensitiv ity and specificity of diagnostic criteria were similar for the two ge nes. Cumulative survival rate for the splice acceptor site mutation (9 0% at 50 years old) was mid-way between that observed with a malignant (Arg403Leu: 42%) and a benign mutation (Arg403Trp: 100%) in the beta myosin heavy chain gene (P=0.002). Conclusions. The detailed phenotype associated with a mutation in the MyBP-C gene was no different from t hat associated with mutations in the beta myosin heavy chain gene, exc ept for prognosis which appeared more benign. These preliminary result s suggest that there is no locus-specific genotype-phenotype correlati on for the two genes analysed.