Abstract
Familial hypertrophic cardiomyopathy (FHCM) is a heterogeneous disease with an autosomal dominant Mendelian inheritance and variable penetrance. Several mutations in the β-myosin heavy chain (βMHC) gene, the first gene identified for this disease, have been described that co-segregate with the inheritance of the disease. All the mutations in the βMHC gene encode for the globular head of the myosin protein except for the deletion mutation which encodes for the carboxy-terminus (rod) of the protein. The clinical features associated with some of the mutations in the βMHC gene have been characterized. A missense mutation in exon 13 of the βMHC gene, is associated with a higher incidence of sudden cardiac death and severe form of the disease, while some others are associated with a more benign form of the disease. Recently, three other loci, on chromosomes 1q3, 11q11 and 15q2, for FHCM have been identified and research is ongoing to identify the candidate genes. Cardiac involvement in Duchenne/Becker muscular dystrophy (DMD), and myotonic dystrophy is common. Heart failure due to dilated cardiomyopathy and sudden cardiac death are the common causes of death in these disorders. The genes responsible for DMD and myotonic dystrophy are dystrophin and myotonin protein kinase genes located on chromosomes X and 19 respectively. The disease in DMD is due to deletion mutations in the dystrophin gene, while myotonic dystrophy is due to expansion of the GCT trinucleotide repeats in the myotonin-protein kinase gene. Familial dilated cardiomyopathy comprises 20% of cases of idiopathic dilated cardiomyopathy. Linkage analyses utilizing highly polymorphic tandem repeat markers are ongoing to map the chromosome locus and ultimately identify the candidate gene(s). Mutations in the mitochondrial DNA have also been reported with hypertrophic and dilated cardiomyopathies.