Bashir R, Britton S, Strachan T, Keers S, Vafiadaki E, Lako M, Richard I, Marchand S, Bourg N, Argov Z, Sadeh M, Mahjneh I, Marconi G, Passos-Bueno M R, Moreira E de S, Zatz M, Beckmann J S, Bushby K
Department of Human Genetics, University of Newcastle upon Tyne, United Kingdom.
Nat Genet. 1998 Sep;20(1):37-42. doi: 10.1038/1689.
The limb-girdle muscular dystrophies are a genetically heterogeneous group of inherited progressive muscle disorders that affect mainly the proximal musculature, with evidence for at least three autosomal dominant and eight autosomal recessive loci. The latter mostly involve mutations in genes encoding components of the dystrophin-associated complex; another form is caused by mutations in the gene for the muscle-specific protease calpain 3. Using a positional cloning approach, we have identified the gene for a form of limb-girdle muscular dystrophy that we previously mapped to chromosome 2p13 (LGMD2B). This gene shows no homology to any known mammalian gene, but its predicted product is related to the C. elegans spermatogenesis factor fer-1. We have identified two homozygous frameshift mutations in this gene, resulting in muscular dystrophy of either proximal or distal onset in nine families. The proposed name 'dysferlin' combines the role of the gene in producing muscular dystrophy with its C. elegans homology.
肢带型肌营养不良症是一组遗传异质性的遗传性进行性肌肉疾病，主要影响近端肌肉组织，至少有三个常染色体显性和八个常染色体隐性位点的证据。后者大多涉及编码肌营养不良蛋白相关复合物成分的基因突变；另一种形式是由肌肉特异性蛋白酶钙蛋白酶3的基因突变引起的。通过定位克隆方法，我们确定了一种肢带型肌营养不良症的基因，我们之前将其定位到2号染色体p13区域（LGMD2B）。该基因与任何已知的哺乳动物基因均无同源性，但其预测产物与秀丽隐杆线虫精子发生因子fer-1相关。我们在该基因中鉴定出两个纯合移码突变，导致九个家族出现近端或远端发病的肌营养不良症。提议的名称“dysferlin”结合了该基因在导致肌营养不良症中的作用及其与秀丽隐杆线虫的同源性。
