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目的:分析比较一对疑为calpain蛋白病变中国姐弟的capn3基因型和临床表型。方法:对其姐进行肌肉活检作病理学检查和calpain-3/dysferlin联合免疫印迹检测。根据文献设计引物,采集该17岁的姐姐和13岁的弟弟外周血进行capn3基因全部24个外显子直接测序,同时行MRI以观察肌肉组织受累情况。结果:本研究为首次对国内肢带型肌营养不良症2A(LGMD 2A)患者进行基因筛查。姐姐表现为典型LGMD症状,伴有翼状肩及跟腱挛缩,MRI亦提示大腿后群肌肉受累;免疫印迹检测结果提示为calpian蛋白病患者。直接测序发现姐弟均携带capn3基因的一个位点错义突变c.146G>A及另一个位点c.329G>A。本研究还对c.329G>A位点在110名正常人血标本进行单核苷酸多态性分析,仅1例携带杂合突变,预测软件提示此位点改变无显著意义。弟弟携带同样的基因突变,但表现为无症状的高磷酸肌酸激酶(CK)血症。结论:calpain蛋白病患者中,相同的基因型可以出现不同的临床表型,不仅可表现为LGMD2A,而且还可以表现为无症状高CK血症。
OBJECTIVE: To analyze and compare the genotypes and clinical phenotypes of capn3 in Chinese siblings suspected of having calpain protein lesions. Methods: Sister sister was examined by muscle biopsy and calpain-3 / dysferlin co-immunoblotting. According to the literature primers were designed, collecting the 17-year-old sister and 13-year-old brother peripheral blood capn3 gene all 24 exons direct sequencing, while MRI to observe muscle tissue involvement. Results: This study was the first to screen genes for LGMD 2A in patients with limb muscular dystrophy in the country. Sister showed typical symptoms of LGMD, with atrioventricular and Achilles tendon contractures, MRI also prompted muscle involvement in the thigh after the group; Western blot results suggest that patients with calpian proteinosis. Direct sequencing found that siblings all carry a site missense mutation of capn3 gene c.146G> A and another site c.329G> A. In this study, single nucleotide polymorphisms (SNPs) of c.329G> A locus were detected in 110 normal human blood samples. Only 1 case of heterozygous mutation was detected in the blood samples. No significant changes were predicted by the software. The younger brother carries the same genetic mutation but manifests asymptomatic hyperkaline phosphate creatine kinase (CK). CONCLUSIONS: Among the patients with calpain proteinosis, the same genotype may show different clinical phenotypes, not only as LGMD2A, but also asymptomatic hypercholesterolemia.