A GENE DEFECT THAT CAUSES CONDUCTION SYSTEM DISEASE AND DILATED CARDIOMYOPATHY MAPS TO CHROMOSOME 1P1-1Q1

Longitudinal evaluation of a seven generation kindred with an inherite d conduction system defect and dilated cardiomyopathy demonstrated aut osomal dominant transmission of a progressive disorder that both pertu rbs atrioventricular conduction and depresses cardiac contractility. T o elucidate the molecular genetic basis for this disorder, a genome-wi de linkage analysis was performed. Polymorphic loci near the centromer e of chromosome 1 demonstrated linkage to the disease locus (maximum m ultipoint lod score = 13.2 in the interval between D1S305 and D1S176). Based on the disease phenotype and map location we speculate that gap junction protein connexin 40 is a candidate for mutations that result in conduction system disease and dilated cardiomyopathy.