Familial dilated cardiomyopathy locus maps to chromosome 2q31.
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.


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
B L
BL
Department of Pediatric Cardiology, Boston Children's Hospital, Boston, MA, USA.
Niimura
H
H
Osborne
J A
JA
Fatkin
D
D
MacRae
C
C
Solomon
S
S
Benson
D W
DW
Seidman
J G
JG
Seidman
C E
CE
D000293:Adolescent; D000328:Adult; D000368:Aged; D002311:Cardiomyopathy, Dilated / Q000235:genetics*; D002648:Child; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree