Genetic linkage analysis identified a new familial dilated cardiomyopathy locus (CMD1G) on chromosome 2q31 (maximum LOD score=4.86), causing early-onset congestive heart failure.
Observational
Effect estimate: LOD score 4.86
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.
Siu et al. (Tue,) conducted a observational in Familial dilated cardiomyopathy. Genetic linkage analysis was evaluated on Identification of causal gene defect / linkage locus (LOD score 4.86). Genetic linkage analysis identified a new familial dilated cardiomyopathy locus (CMD1G) on chromosome 2q31 (maximum LOD score=4.86), causing early-onset congestive heart failure.