摘要：

目的 总结肢带型肌营养不良症2A 型（LGMD2A 型）临床前期的临床表现、实验室检查、影像学检查、神经电生理学检查、基因检测和家系资料等，为LGMD2A 型的早期诊断提供临床依据。方法与结果 2 例男性患儿，均4 岁，幼儿园入学体格检查发现血清肌酸激酶升高（分别为正常参考值上限的25 和60 倍），运动功能良好，例1 伴反复多发性皮疹和背部毛发轻度增多的皮肤损害表现，例2 表现为双侧小腿稍肥大坚实，肌电图和肌肉组织活检均提示肌源性损害，双侧大腿肌肉MRI未见明显异常。二代基因测序显示，2 例患儿均存在CAPN3 基因复合杂合突变：例1 存在复合杂合的错义突变［c.2092C > T（p.Arg606Ser）］和移码突变［c.712delT（p.Phe239LeufsTer14）］，2 个突变位点均未见报道；例2 存在复合杂合的错义突变［c.600C>G（p.Phe200Leu）和c.619A > G（p.Lys207Glu）］，c.600C > G（p.Phe200Leu）突变位点未见报道。Sanger测序证实二者家系均符合常染色体隐性遗传。2 例患儿明确诊断为LGMD2A 型，两家系明确诊断为LGMD2A 型家系。结论 无症状高肌酸激酶血症应考虑LGMD2A 型的可能，本研究增加了人群CAPN3 基因突变的多样性。

关键词: 肌营养不良, 肢带型, 表型, 基因, 突变, 系谱

Abstract:

Objective To explore the clinical manifestations, laboratory examination, imaging, neurophysiological, genetic test and family data of 2 patients with limb-girdle muscular dystrophy type 2A (LGMD2A) during the preclinical stage, and to provide clinical data for the early diagnosis of LGMD2A. Methods and Results Two 4-year-old male patients presented elevated serum creatine kinase (CK) level (25-fold and 60-fold higher than normal levels, respectively), with good motor function. Case 1 had skin damage performance of repeated multiple rashes and mild increased back hair. In Case 2, the patient's double lower legs were slightly enlarged and firm, and EMG and muscle biopsies showed myogenic damage. There was no abnormality in MRI of double thigh muscles. The next-generation sequencing (NGS) showed that there were complex heterozygous mutations in the CAPN3 gene in both cases: Case 1 carried missense [c.2092C > T (p.Arg606Ser)] and frameshift [c.712delT (p.Phe239LeufsTer14)] compound heterozygous mutation and none of the mutations have been reported; Case 2 carried compound heterozygous missense mutations [c.600C > G (p.Phe200Leu) and c.619A > G (p.Lys207Glu)], and the former has not been reported. Sanger sequencing confirmed that the pedigree was autosomal recessive. The clinical diagnosis was LGMD2A, and their families were diagnosed as LGMD2A pedigree. Conclusions The possibility of LGMD2A needs to be considered for asymptomatic high CK. In addition, this study increased the diversity of CAPN3 gene mutations in the population.

Key words: Muscular dystrophies, limb-girdle, Phenotype, Genes, Mutation, Pedigree