TANC2基因变异2例患儿的临床及遗传学分析并文献回顾  

Clinical and genetic analysis of two children with TANC2 gene variants and a literature review

作　　者：楚嫚嫚 徐丹[1] 谢加阳 张晓莉[1] 王梦月 李佳霖 马轶超 李小丽[1] 王俊玲 贾天明[1] Chu Manman;Xu Dan;Xie Jiayang;Zhang Xiaoli;Wang Mengyue;Li Jialin;Ma Yichao;Li Xiaoli;Wang Junling;Jia Tianming(Department of Pediatrics,the Third Affiliated Hospital of Zhengzhou University,Zhengzhou,Henan 450052,China)

机构地区：[1]郑州大学第三附属医院儿内科,郑州450052

出　　处：《中华医学遗传学杂志》2024年第10期1195-1200,共6页Chinese Journal of Medical Genetics

基　　金：河南省医学科技攻关计划联合共建项目(LHGJ20200439)。

摘　　要：目的探讨2例TANC2基因变异所致神经发育障碍性疾病(NDDs)患儿的临床及遗传学特征。方法回顾性分析于2020年4月和2021年4月就诊于郑州大学第三附属医院小儿神经内科的2例NDDs患儿的临床资料。采集患儿及其父母的外周血样,进行全外显子组测序,对候选变异进行Sanger测序家系验证。以"TANC2基因""神经发育障碍性疾病"为中文关键词,以"Neurodevelopmental disorders""Nervous system development disorders""TANC2"为英文关键词,检索时间为建库至2023年12月,在中国知网、万方数据知识服务平台、PubMed数据库检索相关病例进行回顾性分析。本研究通过郑州大学附属第三医院医学伦理委员会的审查[伦理号:(2020)医伦审第57号]。结果例1为1岁3月龄女性,1岁时出现抽搐发作,共3次,口服奥卡西平治疗后抽搐缓解,2岁7个月时停用奥卡西平,语言、运动及智力发育基本正常。例2为1岁10月龄男性,1岁时出现抽搐发作,表现为肌阵挛发作,发作频繁,加用丙戊酸钠治疗后抽搐得到控制。患儿语言、运动及智力均落后约半年。基因测序显示例1和例2分别存在TANC2基因(NM_025185.4)c.3398G>A(p.Gly1133Glu)和c.2829+1G>A新发变异。根据美国医学遗传学与基因组学学会(ACMG)相关变异指南,前者评级为可能致病性变异(PS2+PM2_Supporting+PP3),后者评级为致病性变异(PVS1+PS2+PM2_Supporting)。共检索到国外文献2篇,共17个病例,16种TANC2基因变异位点,包括剪接变异4种(25.0%)、移码变异8种(50.0%)、无义变异4种(25.0%)。常见表现包括自闭症谱系障碍(70.6%,12/17)、智力障碍(94.1%,16/17)、语言发育迟缓(88.2%,15/17)、运动发育迟缓(58.8%,10/17)、特殊面容、癫痫、共济失调、胸廓以及脊柱畸形等。结论TANC2基因变异考虑为2例NDDs患儿癫痫及发育迟缓的遗传学病因。ObjectiveTo explore the clinical and genetic characteristics of two children with Neurodevelopmental disorders(NDDs)due to variants of TANC2 gene.MethodsClinical data of two children who were admitted to the Third Affiliated Hospital of Zhengzhou University respectively in April 2020 and April 2021 were retrospectively analyzed.Peripheral blood samples of the children and their parents were collected and subjected to whole exome sequencing.Candidate variants were verified by Sanger sequencing.By using"TANC2 gene","Neurodevelopmental disorders","Nervous system development disorders","TANC2"as the key words,similar cases were searched from the CNKI,Wanfang database platform and PubMed database,with the search time set as from the establishment of the database to December 2023.This study was approved by Medical Ethics Committee of the Third Affiliated Hospital of Zhengzhou University(Ethics No.2020-57).ResultsCase 1 was a 1-year-and-3-month-old girl who had developed convulsions at 1 year old and had three episodes of seizures.Her epilepsy had resolved with the treatment of oxcarbazepine,which was stopped at the age of 2-year-and-7-month.Her language,movement and intelligence development were all normal.Case 2 was a 1-year-and-10-month-old boy,who had developed convulsions at 1 year old.His seizure type was myoclonus,and the frequency was dozens of times a day.His epilepsy had resolved with the treatment of sodium valproate.His language,movement and intelligence development was delayed for about half a year.Genetic analysis showed that both children had harbored novel variants of the TANC2 gene(NM_025185.4),including c.3398G>A(p.Gly1133Glu)and c.2829+1G>A,respectively.Based on the guidelines from the American College of Medical Genetics and Genomics(ACMG),the former was rated as likely pathogenic(PS2+PM2_Supporting+PP3)and the latter was rated as pathogenic(PVS1+PS2+PM2_Supporting).Two previous reports were retrieved,which had involved 17 cases and 16 variants.Common features had included autism spectrum disorder(70

关 键 词：神经发育障碍 TANC2基因 癫痫 儿童 

分 类 号：R741[医药卫生—神经病学与精神病学]