ATXN8OS基因三核苷酸重复扩展突变的脊髓小脑性共济失调患者临床表型特征分析  

Phenotype analysis of patients of spinocerebellar ataxia with trinucleotide repeat expansion of ATXN8OS gene

作　　者：王丽[1,2] 郝莹 段晓慧[1] 张瑾[1] 顾卫红[1] Wang Li;Hao Ying;Duan Xiaohui;Zhang Jin;Gu Weihong(Department of Neurology,China-Japan Friendship Hospital,Beijing 100029,China;Department of Neurology,the First Hospital ofTsinghua University,Beijing 100016,China)

机构地区：[1]中日友好医院神经科,北京100029 [2]清华大学第一附属医院神经内科,北京100016

出　　处：《中华神经科杂志》2020年第8期575-581,共7页Chinese Journal of Neurology

摘　　要：目的探讨ATXN8OS基因CTA/CTG三核苷酸重复扩展突变患者的临床表型与遗传学特征。方法研究对象为中日友好医院神经科运动障碍与神经遗传病研究中心2005—2017年收集的1689例临床拟诊为脊髓小脑性共济失调(SCAs)的患者。首先排除其SCA1、SCA2、SCA3、SCA6、SCA7、SCA17和DRPLA基因动态突变,之后对ATXN8OS基因非编码区CTA/CTG三核苷酸重复序列进行分析检测,并与100名健康对照进行对比。针对携带扩展突变的患者进行临床表型及遗传特征分析。结果共发现有21例患者携带异常扩展的ATXN8OS基因CTA/CTG重复序列,其中CTA/CTG三核苷酸重复扩展≥80次者18例,常见首发症状为走路不稳,逐渐出现言语不清、饮水呛咳,4例患者伴有头部或肢体震颤;CTA/CTG三核苷酸重复扩展70~79次者3例,首发症状为走路不稳,逐渐出现言语不清,尚无饮水呛咳,不伴有震颤。100名健康对照的ATXN8OS基因CTA/CTG重复扩展为19~42次。头颅MRI检查21例患者除1例显示胼胝体发育不良外,其余均显示中到重度小脑萎缩,部分患者脑干轻度萎缩。结论携带ATXN8OS基因CTA/CTG重复扩展突变的大部分SCA患者具有共济失调、构音障碍等临床表型,头部MRI显示明显小脑萎缩,提示该突变与SCA8基因相关。Objective To investigate the clinical and genetic characteristics of patients with CTA/CTG trinucleotide repeat expansion of ATXN8OS gene.Methods The CTA/CTG trinucleotide repeats of ATXN8OS gene were detected in 1689 spinocerebellar ataxia cases from Research Center for Movement Disorders and Neurogenetics,Department of Neurology,China-Japan Friendship Hospital in 2005—2017.The correlation between clinical phenotypes and expanded CTA/CTG repeats in the ATXN8OS gene of patients was studied carefully,and compared with 100 healthy controls.Results Twenty-one patients with pathological CTA/CTG repeat expansion of ATXN8OS gene were collected.Eighteen of them carried the alleles with more than 80 repeats,whose common initial symptom was gait instability,followed by dysarthria and dysphagia with disease progression.Four of the 18 patients presented with head or truncal tremor.The other three patients carried the alleles with the repeats ranging from 70 to 79,whose initial symptom was walking instability,gradually appeared dysarthria,with no dysphagia or tremor.The repeat lengths ranged from 19 to 42 in the 100 healthy controls.The brain magnatic resonance imaging of almost all the patients showed moderate to severe cerebellar atrophy,and some patients with mild atrophy of the brainstem except one case with corpus callosum dysplasia.Conclusions Most of the patients with CTA/CTG repeat expansion presented with ataxia and dysarthria.Brain magnetic resonance imaging showed significant cerebellar atrophy,suggesting that the mutation is related to SCA8 gene.

关 键 词：脊髓小脑共济失调 基因 突变 表型 

分 类 号：R744.7[医药卫生—神经病学与精神病学]