Copyright © 1998 by the European Society of Cardiology.
Genotype–phenotype correlations in familial hypertrophic cardiomyopathy
A comparison between mutations in the cardiac protein-C and the beta-myosin heavy chain genes
a Service de Cardiologie, Hôpital Pitié-Salpêtrière, Paris
b INSERM UR 153, Hôpital Pitié-Salpêtrière, Paris
c Service de Cardiologie, Hôpital Ambroise Paré, Boulogne
d Service de Cardiologie, Hôpital Boucicaut, Paris
e Service de Cardiologie, Hôpital Laennec, Nantes
f INSERM U 155, Chateau de Longchamp, Paris, France
accepted May 13, 1997
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 with 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 clinical, electrocardiographic and echocardiographic parameters analysed, the only difference with the beta-MHC group (n=35) was a shorter acceleration time of systolic flow in the pulmonary artery (P<0·05). Sensitivity and specificity of diagnostic criteria were similar for the two genes. Cumulative survival rate for the splice acceptor site mutation (90% 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 that associated with mutations in the beta myosin heavy chain gene, except for prognosis which appeared more benign. These preliminary results suggest that there is no locus-specific genotype–phenotype correlation for the two genes analysed.
Key Words: Hypertrophic cardiomyopathy • MyBP-C gene • myosin • prognosis
f1 Correspondence: Michel Komajda, MD, Service de Cardiologie, Pavillon Rambuteau, Hôpital Pitié-Salpêtrière, 47 Boulevard de l'Hôpital, 75651 Paris cedex 13, France
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