抗肌萎缩蛋白聚糖，一种新的骨骼肌基因，在三泽肌病和肢带型肌营养不良中发生突变。

Dysferlin, a novel skeletal muscle gene, is mutated in Miyoshi myopathy and limb girdle muscular dystrophy.

作者信息

Liu J, Aoki M, Illa I, Wu C, Fardeau M, Angelini C, Serrano C, Urtizberea J A, Hentati F, Hamida M B, Bohlega S, Culper E J, Amato A A, Bossie K, Oeltjen J, Bejaoui K, McKenna-Yasek D, Hosler B A, Schurr E, Arahata K, de Jong P J, Brown R H

机构信息

Day Neuromuscular Research Laboratory, Charlestown, Massachusetts 02129, USA.

出版信息

Nat Genet. 1998 Sep;20(1):31-6. doi: 10.1038/1682.

DOI:10.1038/1682

PMID:9731526

Abstract

Miyoshi myopathy (MM) is an adult onset, recessive inherited distal muscular dystrophy that we have mapped to human chromosome 2p13. We recently constructed a 3-Mb P1-derived artificial chromosome (PAC) contig spanning the MM candidate region. This clarified the order of genetic markers across the MM locus, provided five new polymorphic markers within it and narrowed the locus to approximately 2 Mb. Five skeletal muscle expressed sequence tags (ESTs) map in this region. We report that one of these is located in a novel, full-length 6.9-kb muscle cDNA, and we designate the corresponding protein 'dysferlin'. We describe nine mutations in the dysferlin gene in nine families; five are predicted to prevent dysferlin expression. Identical mutations in the dysferlin gene can produce more than one myopathy phenotype (MM, limb girdle dystrophy, distal myopathy with anterior tibial onset).

摘要

宫下肌病（MM）是一种成年起病的隐性遗传性远端肌营养不良症，我们已将其定位到人类2号染色体的p13区域。我们最近构建了一个跨越MM候选区域的3兆碱基对的P1人工染色体（PAC）重叠群。这明确了MM基因座上遗传标记的顺序，在其中提供了五个新的多态性标记，并将该基因座缩小到约2兆碱基对。五个骨骼肌表达序列标签（EST）定位于该区域。我们报告其中一个位于一个新的全长6.9千碱基对的肌肉cDNA中，我们将相应的蛋白质命名为“dysferlin”。我们描述了九个家族中dysferlin基因的九个突变；其中五个预计会阻止dysferlin的表达。dysferlin基因中的相同突变可产生不止一种肌病表型（MM、肢带型肌营养不良症、胫前起病的远端肌病）。