Familial dilated cardiomyopathy locus maps to chromosome 2q31.
نویسندگان
چکیده
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.
منابع مشابه
Gene mapping of familial autosomal dominant dilated cardiomyopathy to chromosome 10q21-23.
Dilated cardiomyopathy (DCM) is the most common form of primary myocardial disorder, accounting for 60% of all cardiomyopathies. In 20-30% of cases, familial inheritance can be demonstrated; an autosomal dominant transmission is the usual type of inheritance pattern identified. Previously, genetic heterogeneity was demonstrated in familial autosomal dominant dilated cardiomyopathy (FDCM). Gene ...
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Considerable progress has been made to identify genetic causation of dilated cardiomyopathy (DCM). DCM is characterized by left ventricular dilatation and systolic dysfunction, and after known causes have been excluded has been termed idiopathic dilated cardiomyopathy (IDC). Studies of IDC that occurs in families, termed familial dilated cardiomyopathy (FDC) provided the initial phenotypic data...
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عنوان ژورنال:
- Circulation
دوره 99 8 شماره
صفحات -
تاریخ انتشار 1999