Abstract:

Objective To investigate clinical phenotype and gene mutation of dysferlinopathy. Methods The clinical manifestations, laboratory, imaging, neurophysiological examinations, myopathology and genetic test of 3 patients with dysferlinopathy in 2 Chinese families were studied retrospectively. Results Dysferlinopathy has various clinical manifestations and different clinical subtypes which may appear in the same family. Case 1 was diagnosed as Miyoshi myopathy (MM), while her father (Case 2) was asymptomatic high serum creatine kinase (CK). Muscle MRI showed different degrees of fatty replacement. EMG revealed myogenic damage. Histological morphology showed myodystrophy. Immunohistochemical staining showed negative dysferlin expression in membrane of muscle cells. DYSF gene test showed nonsense mutation in exon 4 c.331C > T (p.Gln111Ter; Case 1 and Case 2) and frameshift mutation in exon 54 c.6141delC (Case 1), and nonsense mutation in exon 23 c.2311C > T (p.Gln771Ter) and frameshift mutation in exon 27 c.2870-2874delAGACC (Case 3). Conclusions Dysferlinopathy has clinical
heterogeneity, which is easily misdiagnosed or missed in diagnosis. Detailed history inquiry, negative dysferlin expression in muscle biopsy and DYSF mutation are helpful for clear and classification diagnosis.

Key words: Muscular dystrophies, Phenotype, Genes, Mutation, Pedigree

摘要：

目的 总结Dysferlin 肌病的临床表型和基因突变特点。方法 回顾分析两家系3 例Dysferlin 肌病患者的临床表现、实验室检查、影像学检查、神经电生理学检查、肌肉病理学检查和基因检测结果。结果 Dysferlin 肌病临床表现多样，同一家系表现出不同的临床亚型［例1 为Miyoshi远端型肌营养不良症，例2（例1 之父）为无症状高肌酸激酶血症］；肌肉MRI 表现为不同程度肌肉脂肪化；肌电图呈肌源性损害；组织学形态可见肌营养不良改变，免疫组织化学染色可见肌细胞胞膜dysferlin 表达降低或缺如；基因检测提示DYSF 基因外显子4 c.331C > T（p.Gln111Ter）无义突变（例1和例2）和外显子54c.6141delC 移码突变（例1），以及外显子23 c.2311C > T（p.Gln771Ter）无义突变和外显子27c.2870-2874delAGACC 移码突变（例3）。结论 Dysferlin 肌病存在临床异质性，易误诊和漏诊。详细的病史询问、肌肉组织活检特异性dysferlin 显著降低或缺如、DYSF基因突变，有助于Dysferlin 肌病的明确诊断和分型诊断。

关键词: 肌营养不良, 表型, 基因, 突变, 系谱