COX20基因变异线粒体复合物Ⅳ缺乏症相关的遗传性周围神经病4例病例系列报告及文献复习  

4 cases of hereditary peripheral neuropathy related to complexⅣdeficiency caused by COX20 gene variants:A case series report and literature review

作　　者：胡超平 施亿贇 李西华 赵蕾 周水珍 王艺 HU Chaoping;SHI Yiyun;LI Xihua;ZHAO Lei;ZHOU Shuizhen;WANG Yi(Department of Neurology,Children's Hospital of Fudan University,Shanghai 201102,China)

机构地区：[1]复旦大学附属儿科医院神经科,上海201102

出　　处：《中国循证儿科杂志》2022年第5期378-383,共6页Chinese Journal of Evidence Based Pediatrics

摘　　要：背景原发性线粒体病具有高度的临床和遗传异质性,其中周围神经是线粒体病的常见受累器官之一。目的总结COX20基因变异相关周围神经病的临床表型及遗传学特征。设计病例系列报告。方法回顾性收集2018年5月至2020年5月复旦大学附属儿科医院诊治的COX20基因变异相关周围神经病患儿的临床资料,总结其临床表现、基因检测结果及治疗效果,并以“COX20”、“线粒体复合物Ⅳ缺乏症(ComplexⅣdeficiency)”为关键词检索中英文数据库。检索时间均为从建库至2021年12月。总结已报道COX20基因变异与临床表型的关系。主要结局指标临床表型和COX20基因变异位点。结果4例患儿纳入分析,男、女各2例,其中3例自幼运动发育落后。4例均在儿童期起病,均以行走不稳为首发症状。肌电图均提示多发性周围神经损害改变,感觉神经轴索受累为主。4例患儿均携带COX20基因复合杂合变异,包括错义变异2个,无义变异和移码变异各1个,其中移码变异c.262delG(p.E88Kfs*35)尚未见报道。文献复习目前共报道COX基因变异18个家系22例患儿(包括本文病例),起病中位年龄为5(1.0~17)岁,22例均以行走困难或步态不稳起病,11例(50.0%)有精神运动发育迟滞,病程中14例(63.6%)出现构音障碍,14例(63.6%)出现肌力下降和/或足部畸形,8例(36.4%)出现共济失调,6例(27.3%)出现肌张力障碍,5例(22.7%)存在认知倒退等。21例患儿行神经传导及肌电图检查,19例(90.5%)提示多发性周围神经病变。头颅(18例)及脊髓(10例)MR检查提示,脊髓萎缩4例(40%),小脑萎缩4例(22.2%)。9例患儿已无法独立行走,丧失独立行走能力中位年龄为10(7~21)岁。目前共报道9个变异位点,4种变异类型,其中错义变异5个,剪切变异2个,无义变异和移码变异各1个。结论COX20基因变异患者多早期起病,以周围神经系统病变为主要表现,可合并构音障碍、共济失调、肌张力障Background Primary mitochondrial diseases have high clinical and genetic heterogeneity,and peripheral nervous system is one of the most commonly involved organ.Objective To investigate the clinical and genetic characteristics of hereditary peripheral neuropathy caused by COX20 gene variants.Design Case series report.Methods Four patients with hereditary peripheral neuropathy caused by COX20 gene variants treated in the Children's Hospital of Fudan University from May 2018 to May 2020 were enrolled,and their clinical manifestations,molecular tests,data of treatment and follow-ups were retrospectively reviewed.Also,we searched published articles using keyword of"COX20",and"ComplexⅣdeficiency"in Chinese and English databases from the inception to December 2021.The relationship between COX20 gene variantion and clinical phenotypes was summarized.Main outcome measures COX20 gene variantion sites and clinical phenotypes.Results Four patients including 2 males and 2 females were enrolled.Three patients had delayed motor mile stones.All 4 patients presented with walking instability onset at early childhood,and nerve conduction study revealed poly-peripheral neuropathy especially with sensory axonal damaged.Whole exome sequencing of 4 patients revealed compound heterozygous variants of COX20 gene,including 2 reported missense variants,1 reported nonsense variant and 1 novel variant—c.262delG(p.E88kfs*35)which has never been reported before.Literature review showed 22 patients from 18 families(including our cases)have been reported till now,with the median age of onset at 5 years old(1.0-17 years old).All patients presented with walking difficulty or unsteady gait at onset(22/22,100%).Common clinical manifestations included developmental retardation(11/22,50.0%),dysarthria(14/22,63.6%),muscle weakness with or without foot deformity(14/22,63.6%),ataxia(8/22,36.4%),dystonia(6/22,27.3%),and cognitive regression(5/22,22.7%).Nerve conduction and electromyography tests revealed poly-peripheral neuropathy in most patients(19/

关 键 词：COX20 基因型 周围神经病 复合物Ⅳ缺乏症 线粒体病 

分 类 号：R745[医药卫生—神经病学与精神病学]