Familial dilated cardiomyopathy locus maps to chromosome 2q31. Circulation 1999 Mar 02;99(8):1022-6
Date
03/02/1999Pubmed ID
10051295DOI
10.1161/01.cir.99.8.1022Scopus ID
2-s2.0-0033514986 (requires institutional sign-in at Scopus site) 117 CitationsAbstract
BACKGROUND: Inherited gene defects are an important cause of dilated cardiomyopathy. Although the chromosome locations of some defects and 1 disease gene (actin) have been identified, the genetic etiologies of most cases of familial dilated cardiomyopathy remain unknown.
METHODS AND RESULTS: We clinically evaluated 3 generations of a kindred with autosomal dominant transmission of dilated cardiomyopathy. Nine surviving and affected individuals had early-onset disease (ventricular chamber dilation during the teenage years and congestive heart failure during the third decade of life). The disease was nonpenetrant in 2 obligate carriers. To identify the causal gene defect, linkage studies were performed. A new dilated cardiomyopathy locus was identified on chromosome 2 between loci GCG and D2S72 (maximum logarithm of odds [LOD] score=4.86 at theta=0). Because the massive gene encoding titin, a cytoskeletal muscle protein, resides in this disease interval, sequences encoding 900 amino acid residues of the cardiac-specific (N2-B) domain were analyzed. Five sequence variants were identified, but none segregated with disease in this family.
CONCLUSIONS: A dilated cardiomyopathy locus (designated CMD1G) is located on chromosome 2q31 and causes early-onset congestive heart failure. Although titin remains an intriguing candidate gene for this disorder, a disease-causing mutation is not present in its cardiac-specific N2-B domain.
Author List
Siu BL, Niimura H, Osborne JA, Fatkin D, MacRae C, Solomon S, Benson DW, Seidman JG, Seidman CEMESH terms used to index this publication - Major topics in bold
AdolescentAdult
Aged
Cardiomyopathy, Dilated
Child
Chromosome Mapping
Chromosomes, Human, Pair 2
Female
Genetic Linkage
Humans
Male
Middle Aged
Pedigree
