(Circulation. 1995;92:3387-3389.)
© 1995 American Heart Association, Inc.
Articles |
Localization of a Gene Responsible for Familial Dilated Cardiomyopathy to Chromosome 1q32
From the Baylor College of Medicine, Houston, Tex; Kaiser Permanente Hospital, Los Angeles, Calif (J.M.G.); University of Texas Houston Health Science Center (S.D.); and the University of Utah, Salt Lake City (J.L.A.).
Correspondence to Robert Roberts, MD, Don W. Chapman Professor of Medicine, Professor of Cell Biology, Baylor College of Medicine, 6550 Fannin, MS SM677, Houston, TX 77030. E-mail eyeager@bcm.tmc.edu or dweaver@bcm.tmc.edu.
Background 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.
Methods and Results 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 
2.7 cm/m2 with an
ejection fraction 
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.
Conclusions 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.
Key Words: cardiomyopathy • molecular biology • heart failure • genetics
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