GENE-MAPPING OF FAMILIAL AUTOSOMAL-DOMINANT DILATED CARDIOMYOPATHY TOCHROMOSOME 1OQ21-23

Dilated cardiomyopathy (DCM) is the most common form of primary myocar dial disorder, accounting for 60% of all cardiomyopathies. In 20-30% o f cases, familial inheritance can be demonstrated; an autosomal domina nt transmission is the usual type of inheritance pattern identified. P reviously, genetic heterogeneity was demonstrated in familial autosoma l dominant dilated cardiomyopathy (FDCM). Gene localization to chromos ome 1 (1p1-1q1 and 1q32), chromosome 3 (3p25-3p22), and chromosome 9 ( 9p13-9q22) has recently been identified. We report one family with 26 members (12 affected) with familial autosomal dominant dilated cardiom yopathy in which linkage to chromosome 10 at the 10q21-q23 locus is id entified. Using short tandem repeat polymorphism (STR) markers with he terozygosity > 70%, 169 markers (50% of the genome) were used before l inkage was found to markers D10S605 and D10S201 with a pairwise LOD sc ore = 3.91, theta = 0, penetrance = 100% for both markers. Linkage to 1p1-1q1, 1q32, 3p25-3p22, and 9q13-9q22 was excluded. We conclude that a new locus for pure autosomal dominant FDCM exists, and that this ge ne is localized to a 9 cM region of 10q21-10q23. The search for the di sease causing gene and the responsible mutation(s) is ongoing.