POLG基因突变所致线粒体病五例报道  

Five Chinese patients with mitochondrial diseases caused by POLG gene mutations

作　　者：赵旭彤 候越 郭露 冯淑艳[3] 刘靖[1] 王青青 张巍[1] 袁云[1] 王朝霞[1] Zhao Xutong;Hou Yue;Guo Lu;Feng Shuyan;Liu Jing;Wang Oingqing;Zhang Wei;Yuan Yun;Wang Zhaoxia(Department of Neurology,Peking University First Hospital,Beijing 100034,China)

机构地区：[1]北京大学第一医院神经内科,100034 [2]解放军陆军军医大学第三附属医院神经内科 [3]河南省人民医院神经内科

出　　处：《中华神经科杂志》2018年第12期942-948,共7页Chinese Journal of Neurology

基　　金：北京市科技计划课题(Z151100003915126).

摘　　要：目的报道线粒体DNA γ-多聚酶基因(POLG)突变所致线粒体病的临床、病理和基因改变特点。方法回顾性分析2012年4月至2018年1月在北京大学第一医院就诊的来自不同家系的5例线粒体病患者的临床资料,对患者进行肌肉,神经活体组织检查(活检)和靶向二代测序基因检测。结果5例患者中男性3例,女性2例。2例显性遗传,3例呈散发或隐眭遗传。发病年龄在15。40岁,病程1~26年。其中1例表现为不典型感觉性共济失调神经病伴构音障碍及眼外肌麻痹综合征伴随心脏预激综合征;有2例和1例分别表现为常染色体显性和隐性遗传性进行性眼外肌瘫痪叠加综合征;1例表现为认知发育延迟伴感觉神经病。伴随肌肉损害的4例患者肌活检均可见线粒体肌病的病理改变。表现为认知发育延迟伴感觉共济失调神经病患者的腓肠神经活检示慢性轴索性神经病。POLG基因在3例散发/隐性遗传患者为复合杂合突变,在2例显性遗传患者为单一杂合突变。其中c.914G>A、c.924G>T、c.1612G>T、c.1613A>T、c.1790G>A和c.3002delG为尚未报道的新突变。结论POLG基因突变可导致不同的临床谱系。在POLG相关的线粒体神经肌肉病中,眼外肌瘫痪、肢体力弱和感觉轴索性周围神经病常见。新发现的POLG基因突变扩展了该基因的突变谱。Objective To report the clinical features,myopathological changes,and gene mutations in five Chinese patients with mitochondrial diseases caused by POLG gene mutations.Methods Clinical materials of five unrelated patients who were referred to Department of Neurology,Peking University First Hospital from April 2012to January 2018,carrying POLG gene mutations,were retrospectively analyzed. Muscle/nerve biopsies and targeted second-generation gene sequencing were performed on the patients.Results Among the five patients,three were male and two were female.Two cases were dominant inheritance and three were sporadic or recessive inheritance.The ages of onset were from 15 to 40years with disease course of one to 26years.One of them showed atypical SANDO (sensory ataxic neuropathy,dysarthria,and ophthalmoparesis)syndrome accompanied by cardiac preexcitation syndrome.There were two cases with autosomal dominant and one case with recessive progressive external ophthalmoplegia plus syndrome.One case presented with cognitive delay and sensory neuropathy.The pathological changes of mitochondrial myopathy were observed in all four patients with muscle involvement.Sural nerve biopsy in the patient with cognitive delay and sensory ataxia revealed chronic axonal pathological changes.POLG gene mutations were found in all five patients by targeted next generation sequencing,including single heterozygous mutations in two dominant inherited patients (c.914G>A and c.2864A>G,respectively),and compound heterozygous POLG gene mutations in the other three sporadic/recessive inherited patients (c.2591A>G/c.1790G>A, c.924G>T/c.3002 delG and c.1613A>T/c.1612G>T,respectively).There were six novel mutations not reported before,i.e.,c.914G>A(p.S305N),c.924G>T(p.Q308H),c.1613A>T(p.E538V),c.1612G>T(p.E538^*), c.1790G>A(p.R597Q)and c.3002 delG.Conclusions POLG gene mutations can lead to different clinical spectrums.Progressive external ophtha/moplegia,limb weakness and axonal sensory neuropathy are commonpresentations in this group of patients wi

关 键 词：线粒体病 DNA聚合酶γ POLG基因 进行性眼外肌瘫痪 感觉轴索性感觉神经病 

分 类 号：R596[医药卫生—内科学]