ATP1A3基因突变致儿童期起病快发病性肌张力障碍-帕金森综合征一家系并文献复习  

A childhood-onset rapid-onset dystonia parkinsonism family with ATP1A3 gene mutation and literatures review

作　　者：张慈柳[1] 尹飞[1] 何芳[1] 盖楠[1] 石自清 彭镜[1] 

机构地区：[1]中南大学湘雅医院儿科湖南省儿童智力障碍研究中心,长沙410008

出　　处：《中华儿科杂志》2017年第4期288-293,共6页Chinese Journal of Pediatrics

基　　金：国家自然科学基金（81371434、81370771）

摘　　要：目的 总结ATP1 A3基因突变所致儿童期起病的快发病性肌张力障碍-帕金森综合征（RDP）一家系临床特点及其治疗和预后情况,并进行文献复习.方法 对2016年1月在中南大学湘雅医院儿科住院治疗的RDP患儿及其家系的临床资料进行总结,通过亚全外基因芯片捕获、二代测序及一代测序验证对其进行基因检测.并以“Rapid-onset dystonia parkinsonism”“RDP”“DYT12”及“快发病性肌张力障碍-帕金森综合征”为检索词查阅在线人类孟德尔遗传数据库（OMIM）和PubMed数据库及CNKI数据库、万方数据库建库至2016年10月相关文献并与本家系合并进行总结.结果 先证者男,2015年4月（3岁4月龄）发热后迅速出现失语、四肢活动障碍、持物不稳,于外院予以营养神经、肢体康复训练后,语言逐渐改善,遗留行走姿势异常.2016年1月（4岁1月龄）发热,再度出现失语、吞咽困难及全身无力伴有头腿梯差（无力症状头部重于上肢重于下肢）,1d内达高峰,并出现四肢强直不伴意识障碍的“抽搐”发作共4次.先证者外祖父、母系亲表兄妹,其母亲（36岁）及兄长（14岁）均于学龄前期一次感染后出现无力,后症状有所好转,但持续存在行走姿势异常及构音障碍,未出现二次发作,智力较正常人落后.其母亲有一弟弟及妹妹,均体健.除兄长外,先证者无其他兄弟姐妹.基因结果分析显示先证者及其母亲、兄长均存在ATP1 A3基因p.R756H位点杂合错义突变.该突变位点国外已有文献报道,为RDP的致病突变,保守性高.先证者及其兄长予苯二氮类药物治疗有效,其中以先证者疗效更为显著,但临床症状未见完全改善,其母治疗依从性差,未见明显疗效.文献检索未见中文文献报道,国外一共报道了51例患者（其中包括6个家系共35例患者及16例散发患者）,加上本组3例,共54例患者中发现14个致RDP的ATP1 A3基因突变位点,其中包括1Objective To explore clinical characteristics,treatment,and prognosis of a family with childhood-onset rapid-onset dystonia parkinsonism （RDP） caused by ATP1A3 gene mutation and review literatures.Method The clinical data of a RDP child,his brother and mother had been analyzed retrospectively.This family was admitted to Xiangya Hospital in January 2016.DNA samples were analyzed by the next-generation sequencing and confirmed by Sanger sequencing.Related literature from PubMed,Online Mendelian Inheritance in Man （OMIM）,CNKI and Wanfang databases to date （up to October 2016）with ＆quot;Rapid-onset dystonia-parkinsonism RDP DYT12＆quot; as key words was reviewed.Result The proband boy was three years and four months old （April 2015） when he had the first attack of the disease.After a febricity,he suddenly acquired acute aphasia and limb movement disorder.Rehabilitation therapy and supportive treatment made his speech gradually recovered but still slurred.However,his abnormal walking posture still existed.Nine months later （January 2016,4 years and one months old）,symptoms including aphasia,dysphagia,and weakness with rostrocaudal gradient reoccured after fever.The disease progressed to the critical condition within 24 hours.He ＆quot;seizured＆quot; four times with tonic spasms of limbs but without loss of consciousness.Family history showed his grandparents were consanguineous marriage.His mother and brother also developed abnormal gait and dysarthria after an infection before primary school age.Their symptoms improved gradually without relapsing.However,they did not recover entirely with mild intellectual disability.His mother had a healthy brother and sister.This proband had no other siblings but the brother.Heterozygous missense mutation p.R756H in ATP1A3 gene was detected in this proband,his mother and his brother.This mutation had been reported pathogenically related to RDP,and it located in highly conserved gene region.Benzodiazepine was used for the proband and his brother,with the pr

关 键 词：张力障碍 基因 突变 儿童 学龄前 

分 类 号：R748[医药卫生—神经病学与精神病学]