NEB基因突变致杆状体肌病的临床、肌肉病理和基因突变特点  

Clinical, muscle pathology and gene mutation characteristics of nemaline myopathy caused by mutations in NEB gene

作　　者：赵丹丹[1] 王光裕 戴廷军[1] 焉传祝[1] 林鹏飞[1] Dandan Zhao;Guangyu Wang;Tingjun Dai;Chuanzhu Yan;Pengfei Lin(Department of Neurology,Qilu Hospital of Shandong University,Jinan 250012,China)

机构地区：[1]山东大学齐鲁医院神经内科,济南250012

出　　处：《中华神经科杂志》2022年第11期1270-1276,共7页Chinese Journal of Neurology

基　　金：山东大学临床研究项目(2020SDUCRCC023)。

摘　　要：目的探讨NEB基因突变致杆状体肌病的临床、肌肉病理和基因突变特点。方法回顾性分析2019-2021年于山东大学齐鲁医院神经肌肉病理研究室确诊的3例杆状体肌病患者的临床表现、辅助检查、肌肉病理和基因检测的结果, 同时结合相关文献进行复习。结果 3例患者均为青春期起病, 起病症状均为双下肢无力, 体格检查均可见高腭弓和狭长脸, 肌电图提示肌源性损害。3例患者的肌肉活组织检查(活检)均可见肌营养不良样表现和肌纤维内杆状体结构堆积。病例1 ATP酶染色可见Ⅰ型纤维优势和群组化。基因检测发现病例1存在NEB基因c.21522+3A>G和c.3471dupC(p.N1158Qfs*5)2种突变;病例2存在c.21522+3A>G和c.1899118992delAG(p.Q6332Afs*8)复合杂合突变;病例3存在c.21522+3A>G和c.3448A>T(p.K1150*)复合杂合突变。3例患者的NEB基因均存在c.21522+3A>G突变, 文献复习发现该突变仅在中国人群中有报道;c.3471dupC(p.N1158Qfs*5)、c.1899118992delAG(p.Q6332Afs*8)和c.3448A>T(p.K1150*)经查阅文献目前国内外均无报道。根据美国医学遗传学与基因组学学会指南的相关内容, c.21522+3A>G、c.3471dupC(p.N1158Qfs*5)、c.3448A>T(p.K1150*)和c.1899118992delAG(p.Q6332Afs*8)均被评级为致病变异。结论杆状体肌病的起病年龄和症状表现具有异质性, 肌肉活检和基因检测是杆状体肌病最重要的诊断方法。NEB基因c.21522+3A>G突变可能在中国人群中是较常见的突变。Objective To investigate the clinical,muscle biopsy and gene mutation characteristics of nemaline myopathy caused by the NEB gene variants.Methods A retrospective analysis of the clinical manifestations,auxiliary examinations,muscle biopsies and genetic analysis of 3 nemaline myopathy patients carrying NEB gene mutations diagnosed in the Neuromuscular Pathology Laboratory of Qilu Hospital of Shandong University during 2019-2021 was done.And the related literature was reviewed.Results All of the 3 patients were congenital onset.The onset symptoms of the 3 patients were weakness of bilateral lower limbs.Physical examinations showed high palatine arches and long narrow faces.Electromyography showed myogenic impairment.Muscle biopsies of the 3 patients revealed myodystrophic changes and nemaline bodies.The ATPase staining of patient 1 showed the predominance and grouping of type 1 muscle fibers.Genetic tests revealed patient 1 carried c.21522+3A>G and c.3471dupC(p.N1158Qfs*5)mutations in the NEB gene,patient 2 carried c.21522+3A>G and c.18991_18992delAG(p.Q6332Afs*8)compound heterozygous mutations and patient 3 carried c.21522+3A>G and c.3448A>T(p.K1150*)compound heterozygous mutations.All the 3 patients carried the c.21522+3A>G mutation in the NEB gene,which had only been reported in Chinese population.The c.3471dupC(p.N1158Qfs*5),c.18991_18992delAG(p.Q6332Afs*8)and c.3448A>T(p.K1150*)mutations have not been reported yet.According to American College of Medical Genetics and Genomics guideline,c.21522+3A>G,c.3471dupC(p.N1158Qfs*5),c.3448A>T(p.K1150*)and c.18991_18992delAG(p.Q6332Afs*8)mutations were all rated pathogenic.Conclusions The onset age and clinical symptoms of nemaline myopathy are heterogeneous.Muscle biopsy and genetic analysis are important for diagnosis of nemaline myopathy.The c.21522+3A>G mutation in the NEB gene may be more common in Chinese population.

关 键 词：杆状体肌病 杆状体 NEB基因 肌肉活组织检查 基因突变 

分 类 号：R746[医药卫生—神经病学与精神病学]