LOCALIZATION OF A GENE RESPONSIBLE FOR FAMILIAL DILATED CARDIOMYOPATHY TO CHROMOSOME 1Q32

Background Dilated cardiomyopathy, characterized by ventricular dilata tion and decreased systolic contraction, is twofold to threefold more common as a cause of heart failure than hypertrophic cardiomyopathy an d costs several billion dollars annually. The idiopathic form occurrin g early in life, with a 75% mortality in 5 years, is a common reason f or transplantation. It is estimated that at least 20% of cases are fam ilial. Methods and Results A family of 46 members spanning for generat ions underwent history and physical examinations, echocardiographic an alysis, and blood sampling for genotyping. Diagnostic criteria, detect ed by echocardiography, consisted of ventricular dimension of greater than or equal to 2.7 cm/m(2) with an ejection fraction less than or eq ual to 50% in the absence of other potential causes. DNA from all memb ers was analyzed by polymerase chain reaction for amplification of sho rt tandem-repeat polymorphic markers located every 10 cM throughout th e human genome. Assuming a penetrance of 90%, linkage analysis was per formed to map the responsible chromosomal locus. Linkage analysis, aft er 412 markers were analyzed, indicated the locus to be on chromosome 1q32, with a peak multipoint logarithm of the odds score at D1S414 of 6.37. Conclusions The locus identified in this study for familial dila ted cardiomyopathy, 1q32, is rich in candidate genes, such as MEF-2, r enin, and helix loop helix DNA binding protein MYF-4. Identification o f the genetic defect could provide insight into the molecular basis fo r the cardiac dilatory response in both familial and acquired disorder s.