ETFDH基因突变致核黄素反应性脂质沉积性肌病18例临床、病理和基因突变特点分析  

Clinical,pathological and gene mutation characteristics of 18 cases of riboflavin-responsive lipid storage myopathy caused by ETFDH gene mutation

作　　者：钱琪[1] 崔文豪 瞿千千[1] 刘海燕 陈萍[1] 周亚光 吕海东[1] QIAN Qi;CUI Wenhao;QU Qianqian(Department of Neurology,Jiaozuo People’s Hospital,Jiaozuo 454002,China)

机构地区：[1]河南省焦作市人民医院神经内科,河南焦作454002

出　　处：《中风与神经疾病杂志》2022年第9期772-776,共5页Journal of Apoplexy and Nervous Diseases

基　　金：河南省医学科技攻关计划项目(No.LHGJ20191340)。

摘　　要：目的探讨ETFDH基因突变致核黄素反应性脂质沉积性肌病(Riboflavin-responsive lipid storage myopathy,RR-LSM)的临床、病理和ETFDH基因突变特点。方法回顾性分析2009年1月-2020年12月就诊于我院,经肌肉活检病理确诊和基因检测证实的18例RR-LSM患者的临床和病理资料,并采取外周血DNA进行Illumina NovaSeq高通量测序,进行数据读取和生物信息学分析。结果18例患者中男女各9例,发病年龄9~60岁,平均(29.83±13.44)岁,病程1 m~22 y,平均4.5 y。主要临床表现为肢体近端无力和运动不能耐受,伴颈伸肌无力14例,咀嚼肌无力9例,吞咽困难5例,恶心纳差5例,少数患者伴有肌肉疼痛和呼吸困难。本组患者肌肉病理均可见肌纤维内有大量脂质沉积,5例可见少量坏死肌纤维,伴有CD68(+)的巨噬细胞浸润。18例患者经核黄素治疗均获得良好疗效。本组病例均检测到ETFDH基因突变,其中复合杂合突变15例(83.3%),单一杂合突变2例(11.1%),纯合突变1例(5.6%)。共发现20个突变位点,其中频率最高的突变位点为c.770A>G,占等位基因的19.4%(7/36),其次为c.1454C>G,占等位基因的8.3%(3/36)。结论ETFDH基因突变所致的RR-LSM患者以躯干中轴肌和咀嚼肌受累为特点,肌肉病理发现肌纤维内有大量脂质沉积是诊断的重要依据。c.770A>G和c.1454C>G是本组病例ETFDH基因最常见的突变位点。Objective To investigate the clinical,pathological and ETFDH gene mutation characteristics of riboflavin-responsive lipid storage myopathy(RR-LSM)caused by ETFDH gene mutation.Methods The clinical and pathological data of 18 RR-LSM patients who were admitted to our hospital from January 2009 to December 2020 and confirmed by muscle biopsy pathology and gene testing were retrospectively analyzed.The Illumina NovaSeq high-throughput sequencing of peripheral blood DNA was performed for data reading and bioinformatics analysis.Results Among the 18 patients,there were 9 males and 9 females.The age of onset ranged from 9 to 60 years old(mean 29.83±13.44 years).The course of disease ranged from 1 month to 22 years(mean 4.5 years).The main clinical manifestations were proximal limb weakness and movement intolerance,accompanied by cervical extensor weakness in 14 cases,masticatory muscle weakness in 9 cases,dysphagia in 5 cases,nausea and poor appetite in 5 cases,and muscle pain and dyspnea in a few patients.Muscle pathology showed a large amount of lipid deposition in muscle fibers and a small amount of muscle fiber necrosis in 5 cases.Immunohistochemical staining indicated that the necrotic muscle fibers were mainly infiltrated by CD68(+)lymphophagocytes.All 18 patients were treated with riboflavin and had good efficacy.ETFDH gene mutation was detected in all cases in this study,including 15 cases(83.3%)with complex heterozygous mutation,2 cases(11.1%)with single heterozygous mutation,and 1 case(5.6%)with homozygous mutation.A total of 20 mutation sites were found,among which the most frequent mutation site was c.770 A>G,accounting for 19.4%(7/36)of the allele,followed by c.1454 C>G,accounting for 8.3%(3/36)of the allele.Conclusion RR-LSM patients caused by ETFDH gene mutation are characterized by trunk axial muscle and masticatory muscle involvement.Muscle pathology found that there are a large number of lipid deposits in muscle fibers is an important basis for diagnosis.c.770 A>G and c.1454 C>G are the most common mu

关 键 词：脂质沉积性肌病 ETFDH基因 临床特点 肌肉病理 

分 类 号：R746.9[医药卫生—神经病学与精神病学]