RFC1基因突变导致伴周围神经病和前庭反射消失的小脑性共济失调综合征1例并文献复习  

Cerebellar ataxia,neuropathy,vestibular areflexia syndrome with replication factor C subunit 1 gene mutation:a case report and literature review

作　　者：付佳钰 刘小璇[1] 傅瑜[1] 何及[1] 张朔[1] 吴捷颖 樊东升[1] Fu Jiayu;Liu Xiaoxuan;Fu Yu;He Ji;Zhang Shuo;Wu Jieying;Fan Dongsheng(Department of Neurology,Peking University Third Hospital,Beijing 100191,China)

机构地区：[1]北京大学第三医院神经内科,北京100191

出　　处：《中华神经科杂志》2022年第7期690-698,共9页Chinese Journal of Neurology

基　　金：北京大学医学部-乌尔姆大学联合项目(PKU2017ZC001-2)。

摘　　要：目的探讨RFC1(replication factor C subunit 1)基因突变导致伴周围神经病和前庭反射消失的小脑性共济失调综合征(CANVAS)患者的临床及遗传学特点,以提高对该疾病的认识。方法报道2021年1月就诊于北京大学第三医院的1例CANVAS患者。从患者外周血提取DNA进行详细的共济失调相关遗传学检测。检索文献中已报道的RFC1基因变异导致的CANVAS,总结分析所有患者的临床及遗传学特点。结果本例患者为51岁女性,主要表现为进行性加重的步态不稳,结合辅助检查符合CANVAS临床诊断。患者基因检测结果除外已报道的其他遗传性共济失调变异,同时完善RFC1基因检测,结果显示患者存在双等位基因致病性变异结构(AAGGG)exp重复扩增。检索国内外报道RFC1基因变异导致CANVAS的文献共14篇,整体CANVAS患者RFC1基因变异率为68%~100%,散发及家族性CANVAS患者中RFC1基因变异率不同,该基因变异具有种族差异。结论成人起病的晚发型共济失调患者中,通过头颅磁共振联合电生理及前庭功能检查有利于CANVAS的识别,RFC1基因检测对于该病诊断有重要意义。本例CANVAS患者扩大了我国共济失调的疾病谱,证实了RFC1基因突变在中国人群共济失调筛查中具有重要意义。Objective To investigate the clinical and genetic characteristics of cerebellar ataxia,neuropathy,vestibular areflexia syndrome(CANVAS)with replication factor C subunit 1(RFC1)gene mutation to improve the understanding of this disease.Methods A case of CANVAS diagnosed in the Peking University Third Hospital in January 2021 was reported.Detailed genetic analyses of ataxia were performed with DNA extracted from the peripheral blood of the patient.Studies including pathogenic variants of RFC1 gene causing CANVAS were reviewed and the clinical and genetic characteristics of the disease were summarized.Results The patient was a 51-year-old female with the prominent manifestation of progressive walking instability.And the clinical data met the diagnostic criteria of CANVAS.The genetic tests excluded other hereditary ataxia mutations and identified the biallelic expansion of the pathogenic variant structure(AAGGG)exp repeat amplification in RFC1 gene.A total of 14 studies on CANVAS with RFC1 gene mutation were reviewed.The overall mutation rate of RFC1 gene in CANVAS was 68%-100%,and it varied in sporadic and familial CANVAS.And the mutation had ethnic differences.Conclusions Among adult patients with late-onset ataxia,the combination of brain magnetic resonance imaging,electrophysiology tests and vestibular function examination is beneficial to the identification of CANVAS.And the genetic test of RFC1 gene has significant value in the diagnosis of this disease.This patient with CANVAS expands the disease spectrum of ataxia in China,and confirms that RFC1 gene mutation is of great significance in the screening of ataxia disorders in the Chinese population.

关 键 词：小脑共济失调 反射 前庭眼 周围神经 三核苷酸重复扩增 RFC1基因 

分 类 号：R744.7[医药卫生—神经病学与精神病学]