NEB基因突变致杆状体肌病11例临床、病理和基因突变特点分析  

Analysis of clinical,pathological and gene mutation characteristics in 11 cases of nemaline myopathy caused by NEB gene mutation

作　　者：陈萍[1] 瞿千千[1] 钱琪[1] 郑献召[1] 刘海燕 崔文豪 周亚光 吕海东[1] Chen Ping;Qu Qianqian;Qian Qi;Zheng Xianzhao;Liu Haiyan;Cui Wenhao;Zhou Yaguang;Lyu Haidong(Department of Neurology,Jiaozuo People′s Hospital,Jiaozuo 454002,China)

机构地区：[1]焦作市人民医院神经内科,焦作454002

出　　处：《中华神经科杂志》2022年第3期216-222,共7页Chinese Journal of Neurology

基　　金：河南省医学科技攻关计划(LHGJ20191340)。

摘　　要：目的:探讨NEB基因突变所致杆状体肌病患者的临床、病理和基因突变特点。方法:收集1997年1月至2020年1月于焦作市人民医院肌病中心,经肌肉活组织检查(活检)病理和基因检测明确诊断为NEB基因突变所致杆状体肌病患者的临床和病理资料,采用二代测序方法对所有患者进行NEB基因检测,并对基因突变特点进行分析。结果:共收集11例杆状体肌病患者,其中男性8例,女性3例,有6例分别来自2个家系。患者就诊年龄为11~52岁,发病年龄为6~23岁,病程为5~35年。神经系统检查:11例患者中8例有高腭弓长脸型,双上肢肌张力正常,腱反射减低,近端肌力Ⅲ~Ⅴ级,远端肌力Ⅴ级。双下肢肌张力减低,腱反射消失,近端肌力Ⅱ~Ⅳ级,远端肌力Ⅲ~Ⅴ级。均无吞咽困难和呼吸肌受累。11例患者中有7例行肌肉活检,病理检查可见肌纤维大小不等,有萎缩肌纤维和代偿性肥大纤维,偶见变性坏死肌纤维。7例患者均可见不同程度的杆状体聚集。5例患者行电镜检查,均发现肌原纤维间有杆状体聚集,且多位于Z带附近,未发现有核内杆状体。11例患者基因检测结果均发现致病基因NEB,并且共检测到9个不同的突变位点,其中外显子区域突变位点8个,内含子区域突变位点1个。其中c.21522+3A>G位点突变10例,c.1623delT位点突变3例,c.17611C>T位点突变3例。其余位点c.4417C>T、c.2549delA、c.21065dupA、c.3520G>A、c.20943G>A、c.192G>A突变各1例。结论:NEB基因突变所致杆状体肌病的临床表型有较大的异质性,肌肉病理检查发现杆状体聚集是诊断该病的重要依据。内含子区域的c.21522+3A>G位点是本组NEB基因最常见的突变位点,c.17611C>T、c.2549delA、c.3520G>A、c.21065dupA、c.20943G>A和c.192G>A为NEB基因新的突变位点。Objective To investigate the characteristics of clinical,muscle pathology and gene mutation in patients with nemaline myopathy caused by NEB gene mutation.Methods The clinical and pathological data of patients with nemaline myopathy caused by NEB gene were collected from Neuromuscular Center of Jiaozuo People′s Hospital from January 1997 to January 2020.The next generation sequencing was preformed to detect NEB gene in all patients,and characteristics of gene mutation were analyzed.Results Among the 11 patients,there were 8 males and 3 females,and 6 of them came from 2 families.The age of seeing a doctor ranged from 11 to 52 years,the age of onset was from 6 to 23 years,and the course of disease ranged from 5 to 35 years.Neurological examination showed that among the 11 patients,8 patients had high palatal arch and long face.The muscle tone of both upperlimbs was normal,the tendon reflex was depressed,the proximal muscle strength was gradeⅢ-Ⅴ,and the distal muscle strength was gradeⅤ.The muscle tone of both lower extremities was reduced and the tendon reflex was absent.The proximal muscle strength was gradeⅡ-Ⅳand the distal muscle strength was gradeⅢ-Ⅴ.No dysphagia or respiratory muscle involvement was found.Muscle biopsies were performed in 7 of the 11 patients,the pathological changes were muscle fibers of different sizes,circular atrophic muscle fibers and compensatory hypertrophic fibers,and occasionally denatured and necrotic muscle fibers were found.Different degrees of rod aggregation could be seen in all the 7 patients.Electron microscopic examination of 5 patients showed that there was rod aggregation between myofibrils,and most of them were located near the Z band,but no intranuclear rod was found.NEB gene was found in all 11 patients,and a total of 9 different mutation sites were detected,including 8 in exon region and 1 in intron region.Among them,c.21522+3A>G was found in 10 cases,c.1623delT was found in 3 cases and c.17611C>T was found in 3 cases.There was 1 case of c.4417C>T,c.2549d

关 键 词：杆状体肌病 NEB基因 病理学 病理学 临床 

分 类 号：R685[医药卫生—骨科学]