Limb-girdle muscular dystrophy type 2G is caused by mutations in the gene encoding the sarcomeric protein telethonin
Limb-girdle muscular dystrophy type 2G is caused by mutations in the gene encoding the sarcomeric protein telethonin
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DOI：
10.1038/72822
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发表时间：
2000-02-01
期刊：
影响因子：
30.8
通讯作者：
Jenne, DE
中科院分区：
文献类型：
--
作者：
Moreira, ES;Wiltshire, TJ;Jenne, DE
常染色体隐性肢带型肌营养不良症（AR LGMD）是一组遗传异质性疾病，主要影响近端肌肉组织（1）。AR LGMD有8种遗传上不同的形式，LGMD 2A-H（参考文献2-10），除LGMD 2G和2 H外，这些形式的遗传病变已被确定。LGMD 2A和LGMD 2B由编码钙蛋白酶3（参考文献11）和dysferlin（参考文献12）的基因突变引起。通常与轻度表型相关（11-13）。编码γ-（参考文献14）、α-（参考文献5）、β-（参考文献6、7）和δ-（参考文献15）-肌聚糖的基因突变分别导致LGMD 2C至2F。肌聚糖与sarcospan、肌营养不良蛋白聚糖、突触营养蛋白和小肌营养不良蛋白一起构成肌营养不良蛋白-糖蛋白复合物（16，17）（DGC）。LGMD 2C-F患者主要有重度临床病程（4-8.13-15.18-20）。在两个巴西家族中，LGMD 2C基因座定位于17 q11 -12的3-cM区间，具有相对轻度的AR LGMD（参考文献9）。为了定位克隆LGMD 2G基因，我们构建了17 q11 -12区域的物理图谱，并将其定位精确到1.2 Mb的间隔。编码telethonin（一种肌节蛋白）的基因位于该候选区域内。我们已经发现telethonin基因突变导致LGMD 2C，确定了AR LGMD的新分子机制。
Autosomal recessive limb-girdle muscular dystrophies (AR LGMDs) are a genetically heterogeneous group of disorders that affect mainly the proximal musculature(1). There are eight genetically distinct forms of AR LGMD, LGMD 2A-H (refs 2-10), and the genetic lesions underlying these forms, except for LGMD 2G and 2H, have been identified. LGMD 2A and LGMD 2B are caused by mutations in the genes encoding calpain 3 (ref. 11) and dysferlin(12). respectively, and are usually associated with a mild phenotype(11-13). Mutations in the genes encoding gamma- (ref. 14), alpha- (ref. 5), beta- (refs 6,7) and delta (ref. 15)-sarcoglycans are responsible for LGMD 2C to 2F, respectively. Sarcoglycans, together with sarcospan, dystroglycans, syntrophins and dystrobrevin, constitute the dystrophin-glycoprotein complex(16,17) (DGC). Patients with LGMD 2C-F predominantly have a severe clinical course(4-8.13-15.18-20). The LGMD 2C locus maps to a 3-cM interval in 17q11-12 in two Brazilian families with a relatively mild form of AR LGMD (ref. 9). To positionally clone the LGMD 2G gene, we constructed a physical map of the 17q11-12 region and refined its localization to an interval of 1.2 Mb. The gene encoding telethonin, a sarcomeric protein, lies within this candidate region. We have found that mutations in the telethonin gene cause LGMD 2C, identifying a new molecular mechanism for AR LGMD.