Identification of gene defects by linkage analysis: use in inherited cardiomyopathies.

Abstract

One of the central activities of current medical (including cardiological) research is identification of the causes of inherited diseases. The goals are the determination of genes and risk factors, introduction of new diagnostic standards and ultimately refinement of therapies. In cardiac disorders, molecular causes have been detected for certain types of hypertrophic cardiomyopathy (HCM), a disease characterized by increased ventricular wall thickness, a high risk of arrhythmias and an increased frequency of sudden cardiac death. The first known cause of HCM was a point mutation in the cardiac beta-myosin heavy chain gene on chromosome 14, detected using a genetic mapping procedure based on linkage of the clinical phenotype with genomic marker sequences. Additional missense mutations have been located in the globular head of beta-myosin, and other disease loci have been identified on chromosomes 1, 11, and 15; the disease genes in these loci have not yet been determined, however.