ANO10基因突变致常染色体隐性脊髓小脑共济失调10型一例表型及基因突变分析  

Clinical and genetic phenotypes of an autosomal recessive spinocerebellar ataxia-10 patient due to ANO10 gene mutations

作　　者：张麟伟[1] 吕朴 张向飞[1] 彭丹涛[1] Zhang Linwei;Lyu Pu;Zhang Xiangfei;Peng Dantao(Department of Neurology,China-Japan Friendship Hospital,Beijing 100029,China)

机构地区：[1]中日友好医院神经科,北京100029

出　　处：《中华神经科杂志》2021年第12期1256-1260,共5页Chinese Journal of Neurology

摘　　要：目的探讨ANO10基因突变所致的常染色体隐性脊髓小脑共济失调10型(SCAR10)1例患者的临床表型及基因突变特点。方法应用全外显子测序技术对中日友好医院神经科2018—2020年收集的30个已排除Friedreich共济失调及继发性共济失调的拟诊为隐性遗传共济失调家系先证者进行全外显子基因检测,结合一代测序对患者及家系成员进行突变位点验证,应用软件对突变位点进行致病性分析,对收集的患者进行详细的神经科体检及辅助检查。结果发现1例ANO10基因突变所致的40岁男性SCAR10患者。该患者临床表现为进行性走路不稳、构音障碍并伴有轻度认知功能减退,外周血辅酶Q10水平减低(0.76μg/ml),头颅磁共振平扫可见小脑明显萎缩。全外显子测序发现该患者ANO10基因存在复合杂合突变:c.1219-2A>C、c.1163-2A>G,均为新突变,一代测序家系验证结果显示2个突变分别来自其表型正常的父母,生物信息学分析结果显示2个剪切区突变均有致病性。结论通过全外显子测序发现了1例ANO10基因复合杂合突变所致的SCAR10患者,该病在中国罕见,常以进行性小脑共济失调为主要表现,多伴有认知功能减退,影像学检查可见明显的小脑萎缩。Objective To investigate the clinical phenotypes,imaging features and pathogenic variants of ANO10 gene related autosomal recessive spinocerebellar ataxia-10(SCAR10).Methods A cohort of 30 probands of autosomal recessive cerebellar ataxia pedigrees from China-Japan Friendship Hospital from 2018 to 2020 were collected.Friedreich ataxia and other causes of acquired ataxia were excluded,then probands were detected by whole-exome sequencing(WES),and potential pathogenic variants were confirmed by Sanger sequencing and validated in all family members.Clinical phenotypes and auxiliary examinations of the patients were analyzed in detail.Results A pedigree of SCAR10 caused by ANO10 gene mutations was identified through WES.The 40-year-old male proband of this pedigree carried compound heterozygous mutations:c.1219-2A>C and c.1163-2A>G of the ANO10 gene,both of which were novel mutations,and Sanger sequencing revealed these two mutations were respectively inherited from his healthy parents.Bioinformatic analysis predicted these two mutations were pathogenic.The proband exhibited progressive unsteady walk,dysarthria,mild cognitive impairment.His plasma total coenzyme Q10 was decreased(0.76μg/ml).Brain magnetic resonance imaging showed remarkable cerebellar atrophy.Conclusions Through WES,a SCAR10 patient caused by novel compound heterozygous mutations of ANO10 gene was identified,which is rare in China.The main clinical manifestation was progressive cerebellar ataxia and cognitive decline,and brain image showed remarkable cerebellar atrophy.

关 键 词：脊髓小脑共济失调 ANO10基因 认知障碍 小脑萎缩 

分 类 号：R744.7[医药卫生—神经病学与精神病学]