共济失调毛细血管扩张综合征家系中ATM基因突变的遗传学分析  

Genetic analysis of ATM gene mutation in ataxia telangiectasia syndrome family

作　　者：袁军鸿 段丽芬[3] 叶磊[3] 钟海燕[3] 张志丹 孙浩[2] 褚嘉祐[2] 杨昭庆[2] YUAN Junhong;DUAN Lifen;YE Lei;ZHONG Haiyan;ZHANG Zhidan;SUN Hao;CHU Jiayou;YANG Zhaoqing(Kunming Medical University,Kunming,Yunnan 650500,China;Department of Medical Genetics,Institute of Medical Biology,Chinese Academy of Medical Sciences&Peking Union Medical College,Kunming,Yunnan 650118,China;Center of Epilepsy,Kunming Children’s Hospital,Kunming,Yunnan 650034,China)

机构地区：[1]昆明医科大学,云南昆明650500 [2]中国医学科学院/北京协和医学院医学生物学研究所医学遗传学研究室,云南昆明650118 [3]昆明市儿童医院癫痫中心,云南昆明650034

出　　处：《中国优生与遗传杂志》2021年第10期1466-1470,共5页Chinese Journal of Birth Health & Heredity

基　　金：云南省高层次卫生健康技术人才培养专项(L-2018003);云南省科技厅昆明医科大学应用基础研究联合专项项目(202001AY070001-273);昆明市卫生健康委员会卫生科研课题(2020-06-01-115);昆明市卫生科技人才培养项目暨“十百千”工程培养计划(2021-SW(省)-23)。

摘　　要：目的对1个共济失调毛细血管扩张综合征(AT)家系的致病基因变异位点进行检测并对其进行遗传学分析。方法对先证者进行临床检查和全外显子组测序;对先证者家系通过PCR-Sanger测序检测可疑变异位点;用I-TASSER软件对含突变位点的外显子区进行生物信息学分析。结果先证者出现双下肢无力、步态不稳、巩膜毛细血管扩张、小脑半球体积减小、免疫缺陷及甲胎蛋白含量异常升高等临床特征。先证者ATM基因(NM_000051)c.6658 C>T(p.Q2220X)检测发现纯合无义突变,其父母均为该位点的杂合突变;蛋白结构生物信息分析表明p.Q2220X无义突变所产生的截短蛋白可能影响ATM基因的激酶活性从而致病。结论本研究确定了该家系中先证者的致病突变位点为ATM基因(NM_000051)c.6658 C>T(p.Q2220X),进一步补充了中国人群中AT的基因突变谱及临床表型谱,为AT的发病机制、临床鉴别等提供了更多参考数据。Objective To detect and genetically analyze the pathogenic gene variants in a family with ataxia telangiectasia syndrome(AT).Methods Clinical examination and whole exome sequencing were performed on the proband.The suspicious mutation sites were detected by PCR-Sanger sequencing in the family members,and the I-TASSER software was used to analyze bioinformatics on the exon regions containing the mutation sites.Results The proband had clinical features such as weakness of both lower limbs,unstable gait,dilatation of scleral capillaries,cerebellar hemisphere volume decrease d,immunodeficiency,and alpha-fetoprotein content abnormally increased.A homozygous nonsense mutation in the ATM gene(NM_000051)c.6658 C>T(p.Q2220X)was detected in the proband,and her parents were heterozygous mutations at this locus.The analysis of protein structure bioinformation indicated that the truncated protein produced by p.Q2220X nonsense mutation might affect the activity of ATM gene kinase,which caused disease.Conclusion It determines that the pathogenic mutation site of the proband in this family is ATM gene(NM_000051)c.6658 C>T(p.Q2220X),which further supplements the gene mutation spectrum and clinical phenotype of AT in the Chinese population.It provides more reference data for the pathogenesis an d clinical identification of AT.

关 键 词：ATM基因 纯合突变 临床异质性 毛细血管扩张 

分 类 号：R741[医药卫生—神经病学与精神病学]