(Circulation. 1999;99:1022-1026.)
© 1999 American Heart Association, Inc.
Clinical Investigation and Reports |
Familial Dilated Cardiomyopathy Locus Maps to Chromosome 2q31
From the Department of Pediatric Cardiology (B.L.S.), Boston Children's Hospital, Boston, Mass; Department of Genetics and Howard Hughes Medical Institute (H.N., J.G.S.), Harvard Medical School, Boston, Mass; and Cardiovascular Division and Howard Hughes Medical Institute (J.A.O., D.F., C.M., S.S., D.W.B., C.E.S.), Brigham and Women's Hospital, Boston, Mass.
Correspondence to Christine E. Seidman, MD, Department of Genetics, Alpert Room 533, Harvard Medical School, 200 Longwood Ave, Boston, MA 02115. E-mail cseidman{at}rascal.med.harvard.edu
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 
=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.
Key Words: cardiomyopathy • genetics • mapping
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