TWNK基因突变致慢性眼外肌麻痹一家系的临床及遗传学分析  

Clinical and genetic analyses of a family with chronic external ophthalmoplegia due to TWNK gene mutation

作　　者：李楠[1] 胡静[1] 赵哲[1] 沈宏锐[1] 邴琪[1] 郭璇 LI Nan;HU Jing;ZHAO Zhe;SHEN Hongrui;BING Qi;GUO Xuan(Second Ward of Neurology Department(Department of Neuromuscular Disease),The Third Hospital of Hebei Medical University,Shijiazhuang,Hebei 050000,China)

机构地区：[1]河北医科大学第三医院神经内科二病区(神经肌肉病科),河北石家庄050000

出　　处：《国际神经病学神经外科学杂志》2024年第3期18-21,共4页Journal of International Neurology and Neurosurgery

摘　　要：慢性进行性眼外肌麻痹是线粒体病的一种表型,以上睑下垂或眼球活动障碍为特征。该文报道一个TWNK基因突变导致的线粒体病家系的临床和遗传学分析。先证者为32岁女性,因“双眼睑下垂10余年”就诊于河北医科大学第三医院神经肌肉病科,仅表现为眼睑下垂、轻度眼外肌麻痹。临床诊断为“慢性进行性眼外肌麻痹”。其家族中也存在类似病例。为明确致病基因,对先证者进行高通量测序及致病变异筛查。根据临床表型与基因测序结果,确定了TWNK基因的一个杂合突变位点(c.1411T>G,p.Y417D)作为候选致病基因。进一步采用Sanger测序法对先证者及其家系成员进行验证,确认了该突变位点的存在。根据美国医学遗传学与基因组学学会遗传变异分类标准与指南,该变异判定为致病变异(PVS1+PM2+PP3),且该位点在国内尚无报道。该研究不仅拓展了TWNK基因的变异谱,还为线粒体病家系的遗传咨询与分子诊断提供了参考依据。Chronic progressive external ophthalmoplegia is a phenotype of mitochondrial disease and is mainly characterized by ptosis or eyeball movement disorder.This article reports the clinical and genetic analyses of a family with mitochondrial disease due to TWNK gene mutation.The proband was a woman aged 32 years,and she attended Department of Neuromuscular Disease,The Third Hospital of Hebei Medical University,due to blepharoptosis of both eyes for more than 10 years,with the manifestations of blepharoptosis and mild external ophthalmoplegia.She was diagnosed with chronic progressive external ophthalmoplegia,and similar cases were observed in her family.High⁃throughput sequencing and pathogenic mutation screening were performed for the proband to identify the pathogenic gene,and based on the clinical phenotype and sequencing results,the heterozygous mutation site(c.1411T>G,p.Y417D)of the TWNK gene was identified as a candidate pathogenic gene.Furthermore,Sanger sequencing was used for the validation of the proband and her family members,and the results confirmed the existence of this mutation site.According to the American College of Medical Genetics and Genomics guidelines,this mutation was determined as a pathogenic mutation(PS1+PM2+PP3),with no previous reports in China.This study further expands the spectrum of TWNK gene mutations and provides a reference for the genetic counseling and molecular diagnosis of families with mitochondrial disease.

关 键 词：眼外肌麻痹 常染色体显性遗传 TWNK基因 线粒体病 

分 类 号：R746[医药卫生—神经病学与精神病学]