MOLECULAR-BASIS OF HYPERTROPHIC AND DILATED CARDIOMYOPATHY

Hypertrophic cardiomyopathy is a heterogeneous disease with autosomal dominant Mendelian inheritance. In 1989, the lst locus for hypertrophi c cardiomyopathy was mapped to cardiac myosin genes located on chromos ome 14q1. Soon, several mutations that cosegregated with inheritance o f the disease were identified in the beta-myosin heavy chain gene, or MHY7. More than 30 missense mutations and 1 deletion mutation in the b eta-myosin heavy chain gene have since been described. Recently, expre ssion of both the mutant beta-myosin heavy chain mRNA and the mutant p rotein has been shown in the cardiac and skeletal muscles of individua ls with hypertrophic cardiomyopathy. Characterization of the clinical features of beta-myosin heavy chain mutations has shown that certain m utations, such as Arg403Gln and Arg719Trp mutations, are associated wi th high rate of sudden cardiac death. In addition to the beta-myosin h eavy chain gene, 3 new loci for hypertrophic cardiomyopathy have recen tly been described, but the candidate genes have not yet been identifi ed. Dilated cardiomyopathy can be inherited as an autosomal dominant, autosomal recessive, and X-linked disease. The familial form of dilate d cardiomyopathy comprises approximately 20 % of the cases of idiopath ic dilated cardiomyopathy Echocardiographic abnormalities such as left ventricular enlargement are present in 10% of asymptomatic relatives. No gene for familial dilated cardiomyopathy has been identified, but linkage studies using polymorphic, short-tandem repeat markers are ong oing. Dilated cardiomyopathy is a common manifestation of Duchenne/Bec ker muscular dystrophy. Heart failure is a common cause of death in th e affected individuals. The gene responsible for this disease is the d ystrophin gene located on X chromosome. There have been reports in the se patients of several dystrophin-gene deletion mutations, which resul t in a decrease in the expression of the dystrophin protein in the car diac and skeletal tissues. X-linked cardiomyopathy, in which the disea se is restricted to the heart, has also been linked to the dystrophin gene. Myotonic dystrophy is an autosomal dominant disease that commonl y involves the myocardium and the conduction tissue, resulting in cond uction defects and heart failure. Sudden cardiac death is the most com mon cause of mortality in patients with myotonic dystrophy. Recently, the myotonin protein kinase gene located on chromosome 19 was identifi ed as the gene responsible for this disease. Expansion of the number o f trinucleotide repeats in the myotonin protein kinase gene results in myotonic dystrophy Mutations in mitochondrial DNA have been associate d with hypertrophic and dilated cardiomyopathy The inheritance of mito chondrial cardiomyopathy is maternal and the disease is associated wit h certain systemic disorders.