A NEW LOCUS FOR ARRHYTHMOGENIC RIGHT-VENTRICULAR DYSPLASIA ON THE LONG ARM OF CHROMOSOME-14

Familial arrhythmogenic right ventricular cardiomyopathy or dysplasia (ARVD) is an idiopathic heart muscle disease with an autosomal-dominan t pattern of transmission, characterized by fibro-fatty replacement of the right ventricular myocardium and ventricular arrhythmias. Recentl y, linkage to the chromosome 14q23-q24 (locus D14S42) has been reporte d in two families. In the present study, three unrelated families with ARVD were investigated. According to strict diagnostic criteria, 13 o f 37 members were considered to be affected. Linkage to the D14S42 loc us was excluded. On the other hand, linkage was found in the region 14 q12-q22 in all three families (cumulative two-point lod score is 3.26 for D14S252), with no recombination between the detected locus and the disease gene. With multipoint linkage analysis, a maximal cumulative led score of 4.7 was obtained in the region between loci D14S252 and D 14S257, These data indicate that a novel gene causing familial ARVD (p rovisionally named ARVD2) maps to the long arm of chromosome 14, thus supporting the hypothesis of genetic heterogeneity in this disease. (C ) 1966 Academic Press, Inc.