Dysferlin肌病两家系三例临床表型及基因突变分析

Analysis on clinical phenotype and gene mutation of three cases of dysferlinopathy in two families

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.6141del C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27 c.2870-2874del AGACC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。

Objective To investigate clinical phenotype and gene mutation of dysferlinopathy.Methods The clinical manifestations, laboratory, imaging, neurophysiological examinations, myopathologyand 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 mayappear in the same family. Case 1 was diagnosed as Miyoshi myopathy（MM）, while her father（Case 2） wasasymptomatic high serum creatine kinase（CK）. Muscle MRI showed different degrees of fatty replacement.EMG revealed myogenic damage. Histological morphology showed myodystrophy. Immunohistochemicalstaining showed negative dysferlin expression in membrane of muscle cells. DYSF gene test showednonsense mutation in exon 4 c.331 C〉 T（p.Gln111 Ter; Case 1 and Case 2） and frameshift mutation in exon54 c.6141 del C（Case 1）, and nonsense mutation in exon 23 c.2311 C 〉T（p.Gln771 Ter） and frameshiftmutation in exon 27 c.2870-2874 del AGACC（Case 3）. Conclusions Dysferlinopathy has clinicalheterogeneity, which is easily misdiagnosed or missed in diagnosis. Detailed history inquiry, negativedysferlin expression in muscle biopsy and DYSF mutation are helpful for clear and classification diagnosis.