一个TAFAZZIN基因新变异引起的Barth综合征患儿家系的遗传学分析  

Genetic analysis of a family with Barth syndrome caused by a novel variant in the TAFAZZIN gene

作　　者：薛莹 宋小艳 赵国栋 贺权泽 张春花 王挺[1] 周琴[2] XUE Ying;SONG Xiaoyan;ZHAO Guodong;HE Quanze;ZHANG Chunhua;WANG Ting;ZHOU Qin(Reproductive and Genetic Center of Suzhou Municipal Hospital,Suzhou,Jiangsu 215000,China;Department of Child Health Care of Suzhou Municipal Hospital,Suzhou,Jiangsu 215000,China;ZJUT Yinhu Research Institute of Innovation and Entrepreneurship Fuyang District,Hangzhou,Zhejiang 311400,China)

机构地区：[1]苏州市立医院生殖与遗传中心,江苏苏州215000 [2]苏州市立医院儿童保健科,江苏苏州215000 [3]杭州市富阳区浙工大银湖创新创业研究院,浙江杭州311400

出　　处：《中国优生与遗传杂志》2024年第3期555-558,共4页Chinese Journal of Birth Health & Heredity

基　　金：江苏省重点研发计划(BE2022736);江苏省妇幼保健重点学科(FXK202142)。

摘　　要：目的对1例患有发育迟缓的男性儿童及其家系进行遗传学分析,明确其病因并为其预后治疗提供依据。方法获取患儿全血进行全外显子高通量测序分析,应用Sanger测序验证患儿及其父母疑似致病基因变异位点,并辅助尿有机酸检测进一步确认。结果患儿窦性心动过速、ST-T改变,全外显子组测序提示TAFAZZIN基因变异,Sanger测序结果显示胎儿携带TAFAZZIN基因c.108del(p.Lys37Serfs*3)半合子变异,为未报道的新变异,其母为c.108del(p.Lys37Serfs*3)杂合变异携带者。尿有机酸分析显示3-甲基戊烯二酸指标轻度升高,3-甲基戊二酸指标升高,综合诊断为Barth综合征。结论TAFAZZIN基因c.108del(p.Lys37Serfs*3)变异是该患儿生长缓慢的致病原因,基因检测结果为该患儿后续治疗及该家系遗传咨询提供依据。Objective To conduct a genetic analysis of a male child with growth retardation and his family,clarify the etiology,and provide a basis for prognosis and treatment.Methods Whole exome high-throughput sequencing analysis was performed on the child's whole blood,and Sanger sequencing was used to validate the suspected pathogenic gene variant sites in the child and his parents,with further confirmation through urinary organic acid testing.Results The child presented with sinus tachycardia and ST-T changes.Whole exome sequencing revealed a variant in the TAFAZZIN gene.Sanger sequencing confirmed the child's fetal heterozygous variant c.108del(p.Lys37Serfs*3),a novel mutation not previously reported.The mother was identified as a carrier of the heterozygous variant c.108del(p.Lys37Serfs*3).Urinary organic acid analysis showed mild elevation in 3-methylglutaconic acid and elevated 3-methylglutaric acid,leading to a comprehensive diagnosis of Barth syndrome.Conclusion The variant c.108del(p.Lys37Serfs*3)in the TAFAZZIN gene is the pathogenic cause of growth retardation in this child.The genetic test results provide a basis for the child's subsequent treatment and genetic counseling for the family.

关 键 词：全外显子组测序 TAFAZZIN基因 新变异位点 Barth综合征 

分 类 号：R725.9[医药卫生—儿科]