(Circulation. 2000;101:473.)
© 2000 American Heart Association, Inc.
Brief Rapid Communications |
Lamin A/C Gene Mutation Associated With Dilated Cardiomyopathy With Variable Skeletal Muscle Involvement
From the University of Colorado Cardiovascular Institute, Denver (G.L.B., L.M.); the Department of Paediatrics, Hammersmith Hospital, Imperial College School of Medicine, London, UK (F.M., C.S.); and ICGEB and Division of Cardiology, Ospedale Maggiore, Trieste, Italy (S.M., G.S.).
Correspondence to Luisa Mestroni, CU-CVI, UCHSC at Fitzsimons, Bldg 500, Room 2115, PO Box 6508, Mail Stop F-442, Aurora, CO 80045-0508. E-mail luisa.mestroni{at}uchsc.edu
Background—Dilated cardiomyopathy is a form of heart muscle disease characterized by impaired systolic function and ventricular dilation. Familial transmission of the disease is frequently observed, and genetic heterogeneity is indicated by clinical and morphological variability in the disease phenotype. In the family MDDC1 reported here, the disease phenotype is severe and characterized by an autosomal dominant pattern of transmission. In addition, the majority of affected family members show signs of mild skeletal muscle involvement.
Methods and Results—On the basis of the clinical observation of both cardiac and skeletal muscle abnormalities in the MDDC1 family, the lamin A/C gene was examined in this kindred. Coding regions were polymerase chain reaction–amplified from genomic DNA and sequenced. A single nucleotide deletion was identified within exon 6, and all affected individuals were found to be heterozygous for this deletion.
Conclusions—Heterozygosity for a single nucleotide deletion in exon 6 of lamin A/C segregates with both the cardiac and skeletal abnormalities observed in the MDDC1 family.
Key Words: cardiomyopathy • genetics • molecular biology • muscles
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