Background-Arrhythmogenic right ventricular dysplasia (ARVD), a familial ca
rdiomyopathy occurring with a prevalence of 1 in 5000, is characterized by
replacement of myocytes with fatty and fibrous tissue. Clinical manifestati
ons 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 inclu
ding history, physical examination, EGG, echocardiogram, right ventricular
angiogram, endomyocardial biopsy, and 24-hour ambulatory EGG. Blood was col
lected for DNA from 149 family members. Analysis of 257 polymorphic microsa
tellite 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 theta=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 n
arrowed to 9.3 cM. Identification of the gene will allow genetic screening
and a specific diagnosis for a disease with protean nonspecific findings. I
t should also provide insight fundamental to understanding cardiac chamber-
specific gene expression and/or the mechanism of myocyte apoptosis observed
in this disease.