Mutations in the Slow Skeletal Muscle Fiber Myosin Heavy Chain Gene (MYH7
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- 作者：Christopher Meredith ; Ralf Herrmann ; Cheryl Parry ; Khema Liyanage ; Danielle E. Dye ; Hayley J. Durling ; Rachael M. Duff ; Kaye Beckman ; Marianne de Visser ; Maaike M. van der Graaff ; Peter Hedera ; John K. Fink ; Elizabeth M. Petty ; Phillipa Lamont ; Vicki Fabian ; Leslie Bridges ; Thomas Voit ; Frank L. Mas
- 刊名：The American Journal of Human Genetics
- 出版年：2004
- 出版时间：October 2004
- 年：2004
- 卷：75
- 期：4
- 页码：703-708
- 全文大小：1184 K
文摘
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.