一个发作性共济失调2型家系的临床表现及CACNA1A基因突变  

Clinical features and CACNA1A gene mutation in a family with episodic ataxia type 2

作　　者：徐迎晖 王智沁 孙启英[1,2] 周琳 许宏伟[1,2] 胡雅岑[1,2] XU Yinghui;WANG Zhiqin;SUN Qiying;ZHOU Lin;XU Hongwei;HU Yacen(Department of Geriatric Neurology,Xiangya Hospital,Central South University,Changsha 410008;National Clinical Research Center for Geriatric Disorders,Xiangya Hospital,Changsha 410008,China)

机构地区：[1]中南大学湘雅医院老年病学神经内科,长沙410008 [2]国家老年疾病临床研究中心(湘雅医院),长沙410008

出　　处：《中南大学学报（医学版）》2022年第6期801-808,共8页Journal of Central South University ：Medical Science

基　　金：湖南省自然科学基金(2020JJ5927)。

摘　　要：发作性共济失调(episodic ataxia,EA)是一组以反复发作性眩晕、构音障碍、共济失调为主要临床特征的疾病。发作性共济失调2型(episodic ataxia type 2,EA2)是EA最常见的亚型,致病基因为CACNA1A,遗传方式为常染色体显性遗传。在中国人群中,CACNA1A突变导致EA2的报道罕见。中南大学湘雅医院于2018年10月收治了1个EA2家系。先证者,男,22岁,因“反复发作性头晕4年,加重1年”入院。临床表现为反复发作性眩晕伴有言语含糊和肢体共济失调,发作间期存在进行性加重的构音障碍,头颅MRI显示小脑萎缩。患者幼年时有神经心理发育障碍表现,成年期认知评估显示存在认知障碍。先证者的母亲和外婆有类似的发作性症状。提取患者及家系成员外周血基因组DNA,对先证者进行全外显子测序,发现杂合移码突变c.2042_2043del(p.Q681Rfs*100)。进一步采用Sanger测序技术对先证者以及家系成员进行该位点测序验证,在先证者及2个家系成员中发现该杂合移码突变,其中1名家系成员携带此突变但无临床表现,提示存在不完全外显。本研究明确了CACNA1A基因c.2042_2043del突变为该EA2家系的致病突变,该突变可能存在不完全外显,在中国汉族人群中为首次报道。本研究丰富了CACNA1A突变相关EA2的临床表型特征,有助于认识该病临床表现及遗传学特点,减少误诊和漏诊。Episodic ataxia(EA)is a group of disorders characterized by recurrent spells of vertigo,truncal ataxia,and dysarthria.Episodic ataxia type 2(EA2),the most common subtype of EA,is an autosomal dominant disease caused by mutation of the CACNA1A gene.EA2 has been rarely reported in the Chinese population.Here we present an EA2 family admitted to Xiangya Hospital in October 2018.The proband was a 22-year-old male who complained of recurrent spells of vertigo,slurred speech,and incoordination for 4 years.Brain magnetic resonance imaging(MRI)showed cerebellar atrophy.He had neuropsychological development disorder in childhood,and cognitive assessment in adulthood showed cognitive impairment.The proband’s mother and grandmother had a similar history.Peripheral blood samples from the proband and family members were collected,and genomic DNA was isolated.Whole exome sequencing of the proband detected a heterozygous frameshift mutation c.2042_2043del(p.Q681Rfs*100)of CACNA1A gene.This mutation was verified in the proband and 2 family members using Sanger sequencing.One family member carrying this mutation was free of symptoms and signs,suggesting an incomplete penetrance of the mutation.We reported a variant c.2042_2043del of CACNA1A gene as the pathogenic mutation in a Chinese EA2 family for the first time.This case enriched the clinical spectrum of CACNA1A related EA2,and contributed to the understanding of clinical and genetic characteristics of EA2 to reduce misdiagnosis.

关 键 词：发作性共济失调2型 CACNA1A基因 临床表现 突变 不完全外显 

分 类 号：R744.7[医药卫生—神经病学与精神病学]