(Circulation. 1998;98:2791-2795.)
© 1998 American Heart Association, Inc.
Brief Rapid Communications |
Localization of a Gene Responsible for Arrhythmogenic Right Ventricular Dysplasia to Chromosome 3p23
From the Section of Cardiology (F.A., D.L., A.K., O.G., T.T., R.H., L.L.B., R.R.), the Department of Pathology (D.W.), and the Graduate Program in Cardiovascular Sciences, the DeBakey Heart Center (F.A.), Baylor College of Medicine, Houston, Tex; the James Paton Memorial Hospital, Gander (P.B.), and the Division of Cardiology, Memorial University of Newfoundland, St John's (M.F.), Newfoundland, Canada; and the Division of Cardiology, Dalhousie University, Halifax, Nova Scotia, Canada (M.G.).
Background—Arrhythmogenic right ventricular dysplasia (ARVD), a familial cardiomyopathy occurring with a prevalence of 1 in 5000, is characterized by replacement of myocytes with fatty and fibrous tissue. Clinical manifestations include structural and functional abnormalities of the right ventricle and arrhythmias, leading to a sudden death rate of 2.5% per year. Four loci have been mapped, but no gene has been identified as yet.
Methods and Results—We identified a large family of >200 members
with ARVD segregating as an autosomal dominant trait affecting 10
living individuals. The diagnosis of ARVD was based on international
diagnostic criteria including history, physical
examination, ECG, echocardiogram, right ventricular
angiogram, endomyocardial biopsy, and 24-hour
ambulatory ECG. Blood was collected for DNA from 149 family members.
Analysis of 257 polymorphic microsatellite markers by
genetic linkage excluded previously known loci for ARVD and identified
a novel locus at 3p23. Analysis of an additional 20 markers
further defined the region. A peak logarithm of the odds score of 6.91
was obtained with marker D3S3613 at 
=0% recombination. Haplotype
analysis identified a shared region between markers D3S3610 and
D3S3659 of 9.3 cM.
Conclusions—A novel locus for ARVD has been mapped to 3p23 and the region narrowed to 9.3 cM. Identification of the gene will allow genetic screening and a specific diagnosis for a disease with protean nonspecific findings. It should also provide insight fundamental to understanding cardiac chamber–specific gene expression and/or the mechanism of myocyte apoptosis observed in this disease.
Key Words: apoptosis • cardiomyopathy • death, sudden • genetics • polymerase chain reaction
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