ETFDH基因变异所致脂质沉积性肌病患者临床表型与遗传学分析  

Clinical and Genetic Analysis of a Patient with Lipid-storage Myopathy Caused by Variations in the ETFDH Gene

作　　者：薛伟 丰岱荣 井冬青 赵鑫 洪帆 李雪梅[1] 刘君玲[1] Xue Wei;Feng Dairong;Jing Dongqing;Zhao Xin;Hong Fan;Li Xuemei;Liu Junling(Department of Neurology,Affiliated Hospital of Weifang Medical University,Weifang 261031,China;Medical Genetics and Prenatal Diagnosis Center,Afiliated Hospital of Weifang Medical University,Weifang 261031,China;Clinical Research Center,Afiliated Hospital of Weifang Medical University,Weifang 261031,China)

机构地区：[1]潍坊医学院附属医院神经内一科,山东潍坊261031 [2]潍坊医学院附属医院医学遗传与产前诊断中心,山东潍坊261031 [3]潍坊医学院附属医院临床研究中心,山东潍坊261031

出　　处：《南开大学学报（自然科学版）》2023年第2期77-84,共8页Acta Scientiarum Naturalium Universitatis Nankaiensis

基　　金：山东省自然科学基金面上项目(ZR2020MH159);山东省高等学校青创科技支持计划(2019KJE006);山东省中医药科技发展计划项目(2019-0423);山东省卫生和计划生育委员会项目(2017WS057)。

摘　　要：脂质沉积性肌病(LSM)是一组以脂质在肌纤维内异常聚集为主要肌肉病理改变的病因异质性疾病,在中国,90%LSM是由晚发型多酰基辅酶A脱氢缺陷(MADD)引起,但确切发病机制尚不完全清楚.本研究报道1例对核黄素反应性脂质沉积性肌病中国患者,分析其疾病表型与基因变异,为晚发型MADD的诊断和治疗提供新的参考依据.结合多种生物信息学分析和突变体的体外功能研究,结果表明先证者的脂质沉积性肌病与ETFDH基因变异导致的MADD有关,肌肉活检与基因检测为LSM的确诊提供了重要证据,补充核黄素可显著改善患者肌无力表型.Lipid storage myopathy(LSM) is an etiologically heterogeneous group of diseases in which abnormal accumulation of lipids in myofibres is the main muscle pathology. 90% of LSM in China is caused by late onset multiple acyl-coenzyme a dehydrogenase deficiency(MADD), but the exact pathogenesis is not fully understood. In this study, a Chinese patient with riboflavin reactive lipid deposition myopathy was reported,and the phenotype and genetic variation of the disease were analyzed, providing a new reference for the diagnosis and treatment of late onset MADD. Combining multiple bioinformatics analyses and in vitro functional studies of the mutant, the results suggest that the lipid deposition myopathy in the prevalent patient was associated with MADD due to ETFDH gene variants, that muscle biopsy and genetic testing provided important evidence for the diagnosis of LSM, and that riboflavin supplementation significantly improved the patient's muscle weakness phenotype.

关 键 词：脂质沉积性肌病 多酰基辅酶A脱氢缺陷 ETFDH基因 核黄素 CoQ10 

分 类 号：R602[医药卫生—外科学]