Recessively inherited limb girdle muscular dystrophy (LGMD) type 2A is the most common LGMD worldwide. Here, we report the first single missense variant in CAPN3 causing dominantly inherited calpainopathy. A 43‐year‐old proband, his father and two sons were heterozygous for a c.1715G>C p.(Arg572Pro) variant in CAPN3. Affected family members had at least three of the following; muscle pain, a LGMD2A pattern of muscle weakness and wasting, muscle fat replacement on magnetic resonance imaging, myopathic muscle biopsy, and elevated creatine kinase. Total calpain 3 protein expression was 4 ± 3% of normal. In vitro analysis of c.1715G>C and the previously described c.643_663del variant indicated that the mutant proteins lack autolytic and proteolytic activity and decrease the quantity of wild‐type CAPN3 protein. Our findings suggest that dominantly inherited calpainopathy is not unique to the previously reported c.643_663del mutation of CAPN3, and that dominantly inherited calpainopathy should be considered for other single variations in CAPN3.

中文翻译：

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单个 c.1715G>C 钙蛋白酶 3 基因变异会导致显性钙蛋白酶病，并失去钙蛋白酶 3 的表达和活性。

隐性遗传的肢带型肌营养不良症 (LGMD) 2A 型是全球最常见的 LGMD。在这里，我们报告的第一单错义变异CAPN3造成显性遗传calpainopathy。在一名43岁的先证者，他的父亲和两个儿子杂的c.1715G> P c ^（Arg572Pro）变种CAPN3. 受影响的家庭成员至少有以下三项；肌肉疼痛、肌肉无力和消瘦的 LGMD2A 模式、磁共振成像上的肌肉脂肪替代、肌病肌肉活检和肌酸激酶升高。总钙蛋白酶 3 蛋白表达为正常值的 4 ± 3%。c.1715G>C 和先前描述的 c.643_663del 变体的体外分析表明突变蛋白缺乏自溶和蛋白水解活性，并减少了野生型 CAPN3 蛋白的数量。我们的研究结果表明，显性遗传calpainopathy是不是唯一的先前报道c.643_663del突变CAPN3，而显性遗传calpainopathy应考虑在其他单一的变化CAPN3。