Hypertrophic cardiomyopathy: failure to demonstrate mutations in exon 13 of the cardiac β myosin heavy-chain gene

1435-1803

Hypertrophiccardiomyopathy ; denaturing gradient gelelectrophoresis ; cardiac beta myosin heavy chain gene ; polymerase chain reaction (PCR)

Springer Online Journal Archives 1860-2000

Medicine

Summary Familial hypertrophic cardiomyopathy (FHCM) has been linked to the cardiac β-myosin heavy-chain (MHC) genes on chromosome 14 (14q1), and a missense mutation within exon 13 of the βMHC gene has been implicated in the pathogenesis of the disease. To test whether this constitutional mutation occurs somatically in the myocardium of the sporadic form of the disease, we studied seven patients with familial (n=3) or sporadic (n=4) hypertrophic cardiomyopathy (HCM). Amplification of exon 13 of the βMHC from paraffin-embedded myocardium using the polymerase chain reaction (PCR) was performed and analysis of the amplified product for migration abnormalities using denaturing gradient gel electrophoresis (DGGE) and direct sequencing of the PCR product were used. Neither patients with HCM nor subjects with dilated cardiomyopathy (DCM) (n=2) exhibited an aberration within exon 13 of the myocardial βMHC. It is concluded that a specific βMHC gene mutation is displayed only in a subset of patients with familial disease, thus further emphasizing the notion of genetic heterogeneity. In addition, in the sporadic form of the disease, somatically occurring mutations in this particular exon could not be demonstrated.

Electronic Resource