Localization of a gene responsible for familial dilated cardiomyopathy to chromosome 1q32

• Published in: Circulation (New York, N.Y.) Vol. 92; no. 12; pp. 3387 - 3389
• Main Authors: DURAND, J.-B, BACHINSKI, L. L, BRUGADA, R, DAIGER, S, GREGORITCH, J. M, ANDERSON, J. L, QUINONES, M, TOWBIN, J. A, ROBERTS, R, BIELING, L. C, CZERNUSZEWICZ, G. Z, ABCHEE, A. B, QUN TAO YU, TAPSCOTT, T, HILL, R, IFEGWU, J, MARIAN, A. J
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 15.12.1995; American Heart Association, Inc
• Subjects: Adolescent; Adult; Aged; Biological and medical sciences; Cardiology. Vascular system; Cardiomyopathy, Dilated - diagnostic imaging; Cardiomyopathy, Dilated - genetics; Child; Chromosome Mapping; Chromosomes, Human, Pair 1; Female; Genetic Linkage; Heart; Humans; Male; Medical sciences; Middle Aged; Myocarditis. Cardiomyopathies; Pedigree; Polymerase Chain Reaction; Ultrasonography; Human; Congestive hypertrophic cardiomyopathy; Gene; Heart disease; Cardiovascular disease; Exploration; Genetics; Molecular biology; Hereditary; Localization; Myocardial disease
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.cir.92.12.3387

Dilated cardiomyopathy, characterized by ventricular dilatation and decreased systolic contraction, is twofold to threefold more common as a cause of heart failure than hypertrophic cardiomyopathy and costs several billion dollars annually. The idiopathic form occurring early in life, with a 75% mortality in 5 years, is a common reason for transplantation. It is estimated that at least 20% of cases are familial. A family of 46 members spanning four generations underwent history and physical examinations, echocardiographic analysis, and blood sampling for genotyping. Diagnostic criteria, detected by echocardiography, consisted of ventricular dimension of > or = 2.7 cm/m2 with an ejection fraction < or = 50% in the absence of other potential causes. DNA from all members was analyzed by polymerase chain reaction for amplification of short tandem-repeat polymorphic markers located every 10 cM throughout the human genome. Assuming a penetrance of 90%, linkage analysis was performed to map the responsible chromosomal locus. Linkage analysis, after 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. The locus identified in this study for familial dilated cardiomyopathy, 1q32, is rich in candidate genes, such as MEF-2, renin, and helix loop helix DNA binding protein MYF-4. Identification of the genetic defect could provide insight into the molecular basis for the cardiac dilatory response in both familial and acquired disorders.