摘要
目的分析常染色体隐性多巴反应性肌张力障碍(AR-DRD)的临床特点及基因突变情况,探讨其治疗效果、随访结果及分子遗传学机制。方法应用高通量测序技术对2016年4月至2017年9月首都儿科研究所附属儿童医院门诊收治的6例否认家族史的运动障碍疾病患儿进行全外显子基因检测,并采用Sanger测序技术进行家系验证分析突变来源。结果1.临床特点:6例患儿均为婴儿期起病,伴肌力下降、肌张力异常,其中以肌张力减低为著。2.基因突变:6例患儿均存在酪氨酸羟化酶(TH)基因突变,5例患儿为复合杂合突变,1例患儿为纯合突变,共检测到5种突变:c.605 G>A 、c.601 C>T、c.364C>T、c.1412_1413insCCCCCAGGCCGTGC和c.646G>A。3.治疗效果:6例患儿经多巴胺治疗后运动功能改善,表现为肌张力及肌力均有不同程度改善。结论携带c.605 G>A突变AR-DRD患儿对多巴胺治疗效果较好,该突变可能为国内外轻中度缺陷型AR-DRD常见变异位点。c.1412_1413insCCCCCAGGCCGTGC移码突变尚未被报道,为本研究新发现的TH基因致病性突变位点。
Objective To analyze the clinical characteristics and gene mutation of autosomal recessive dopa-responsive dystonia(AR-DRD), and to explore its therapeutic effect, follow-up findings and molecular genetic me-chanism. Methods The whole exome sequencing, which based on next-generation sequencing, was performed in 6 movement-disordered patients who denied family history at the outpatient clinic of Children′s Hospital Affiliated to Capital Institute of Pediatrics from April 2016 to September 2017.The mutations identified in probands were then confirmed in probands and their parents by Sanger sequencing in order to analyze the cause of mutations. Results (1)Clinical features: the onset of 6 patients was around infancy, complicated with muscle weakness and abnormal muscle tone.(2)Gene mutation analysis: All 6 patients carried TH gene mutations.Five patients were of complex heterozygosis mutations, 1 patient was of homozygosis mutation.Five mutations were detected: c.605 G>A, c.601 C>T, c.364C>T, c.1412_1413insCCCCCAGGCCGTGC and c. 646G>A.(3)Therapeutic effect: all 6 patients achieved improvement of motor function after dopamine treatment, and they presented the different degrees of improvement in muscle tone and muscle strength. Conclusions The AR-DRD patients who carried c. 605 G>A mutation have a good therapeutic effect treated with L-Dopamine.This mutation may be a common mutation site of mild to moderate defective AR-DRD at home and abroad.The frameshift mutation c. 1412_1413insCCCCCAGGCCGTGC is a new TH gene pathogenicity mutation site discovered by this study.
作者
王珺
王妍
陈汪洋
王立文
Wang Jun;Wang Yan;Chen Wangyang;Wang Liwen(Department of Neurology,Children′s Hospital Affiliated to Capital Institute of Pediatrics,Beijing 100020,China;Kaiumph Medical Diagnostics Co.,Ltd,Beijing 100102,China)
出处
《中华实用儿科临床杂志》
CSCD
北大核心
2019年第10期759-762,共4页
Chinese Journal of Applied Clinical Pediatrics
基金
北京市卫生系统高层次卫生技术人才培养计划(2015-3-084)
首都临床特色应用研究(Z131107002213159).
