Title

Mutations in the slow skeletal muscle fiber myosin heavy chain gene (MYH7) cause laing early-onset distal myopathy (MPD1)

Document Type

Journal Article

Publisher

The University of Chicago Press

School

School of Exercise, Biomedical and Health Science

RAS ID

3612

Comments

Originally published as: Meredith,C., Herrmann,R., Parry,C., Liyanage,K., Dye,D., Durling,H., Duff,R., Beckman,K., de Visser,M., van der Graaff,M., Hedera,P., Fink,J., Petty,E., Lamont,P., Fabian,V., Bridges,L., Voit,T., Mastaglia,F., Laing,N. (2004) Mutations in the slow skeletal muscle fiber myosin heavy chain gene (MYH7) cause laing early-onset distal myopathy (MPD1). American Journal of Human Genetics. 75 (4), 703 -708. Original article available here.

Abstract

We previously linked Laing-type early-onset autosomal dominant distal myopathy (MPD1) to a 22-cM region of chromosome 14. One candidate gene in the region, MYH7, which is mutated in cardiomyopathy and myosin storage myopathy, codes for the myosin heavy chain of type I skeletal muscle fibers and cardiac ventricles. We have identified five novel heterozygous mutations—Arg1500Pro, Lys1617del, Ala1663Pro, Leu1706Pro, and Lys1729del in exons 32, 34, 35, and 36 of MYH7—in six families with early-onset distal myopathy. All five mutations are predicted, by in silico analysis, to locally disrupt the ability of the myosin tail to form the coiled coil, which is its normal structure. These findings demonstrate that heterozygous mutations toward the 3′ end of MYH7 cause Laing-type early-onset distal myopathy. MYH7 is the fourth distal-myopathy gene to have been identified...