Identification of a novel genetic locus for familial cardiac myxomas and Carney complex

Background-Intracardiac myxomas are significant causes of cardiovascular mo rbidity and mortality through embolic stroke and heart failure. In the auto somal dominant syndrome Carney complex, intracardiac myxomas arise in the s etting of lentiginosis and other lesions associated with cutaneous hyperpig mentation, extracardiac myxomas, and nonmyxomatous tumors. Genetic factors that regulate cardiac tumor growth remain unknown. Methods and Results-We used the molecular genetic techniques of linkage ana lysis to study 4 kindreds affected by Carney complex to determine the genet ic basis of this syndrome. Our investigation confirmed genetic heterogeneit y of Carney complex, Moreover, genetic linkage analysis with polymorphic sh ort tandem repeats on the long arm of chromosome 17 revealed maximal pairwi se LOD scores of 5.9, 1.5, 1.8, and 2.9 for families YA, YB, YC01, and YC11 , respectively. Haplotype analysis excluded a founder effect at this locus. These data identify a major 17 cM locus on chromosome 17q2 that contains t he Carney complex disease gene. Conclusions-The ultimate identification and analysis of the Carney complex disease gene at this human chromosome 17q2 locus will facilitate diagnosis and treatment of cardiac myxomas and will foster new concepts in regulation of cardiac cell growth and differentiation.