Meredith Christopher, Herrmann Ralf, Parry Cheryl, Liyanage Khema, Dye Danielle E, Durling Hayley J, Duff Rachael M, Beckman Kaye, de Visser Marianne, van der Graaff Maaike M, Hedera Peter, Fink John K, Petty Elizabeth M, Lamont Phillipa, Fabian Vicki, Bridges Leslie, Voit Thomas, Mastaglia Frank L, Laing Nigel G
Centre for Human Genetics, Edith Cowan University, Perth, Australia.
Am J Hum Genet. 2004 Oct;75(4):703-8. doi: 10.1086/424760. Epub 2004 Aug 20.
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.
我们之前将莱因型早发性常染色体显性遗传性远端肌病（MPD1）与14号染色体上一个22厘摩的区域联系起来。该区域的一个候选基因MYH7，在心肌病和肌球蛋白贮积性肌病中发生突变，它编码I型骨骼肌纤维和心室肌球蛋白重链。我们在6个早发性远端肌病家族中，于MYH7基因的第32、34、35和36外显子中鉴定出5个新的杂合突变——Arg1500Pro、Lys1617del、Ala1663Pro、Leu1706Pro和Lys1729del。通过计算机分析预测，所有这5个突变都会局部破坏肌球蛋白尾部形成卷曲螺旋（其正常结构）的能力。这些发现表明，MYH7基因3'端的杂合突变会导致莱因型早发性远端肌病。MYH7是已被鉴定出的第4个远端肌病基因。
