一个17β-羟类固醇脱氢酶3型缺乏症家系的HSD17B3基因变异分析  

17β-hydroxysteroid dehydrogenase 3 deficiency due to novel compound heterozygous variants of HSD17B3 gene in a sib pair

作　　者：武苏[1] 郑必霞[2] 刘婷 朱子阳[1] 顾威[1] 刘倩琦[1] Wu Su;Zheng Bixia;Liu Ting;Zhu Ziyang;Gu Wei;Liu Qianqi(Department of Endocrinology,Children’s Hospital Affiliated to Nanjing Medical University,Nanjing,Jiangsu 210008,China;Institute of Pediatric Research,Children’s Hospital Affiliated to Nanjing Medical University,Nanjing,Jiangsu 210008,China;The Fourth Clinical School of Nanjing Medical University,Nanjing,Jiangsu 210000,China)

机构地区：[1]南京医科大学附属儿童医院内分泌科,210008 [2]南京医科大学附属儿童医院儿研所,210008 [3]南京医科大学第四临床医学院,210000

出　　处：《中华医学遗传学杂志》2021年第8期787-790,共4页Chinese Journal of Medical Genetics

摘　　要：目的对1个家系中两同胞17β-羟类固醇脱氢酶3型缺乏症患儿的HSD17B3基因进行变异分析,明确其可能的致病原因,为临床诊断提供依据。方法提取2例患儿(先证者和其妹妹)及父母外周血DNA,对性发育相关基因进行panel检测,对可疑变异进行Sanger测序验证及生物信息学分析。结果测序结果显示2例患儿(先证者和妹妹)的HSD17B3基因均存在c.839T>C(p.Leu280Pro)和c.239G>T(p.Arg80Leu)复合杂合变异,两个变异位点均为未报道过的错义变异,Sanger测序验证结果显示其父亲携带c.239G>T杂合变异,母亲携带c.839T>C杂合变异,因此患儿的变异分别来自父母。经PolyPhen2、MutationTaster等在线软件预测均显示c.239G>T和c.839T>C变异均为有害变异。根据美国医学遗传学与基因组学学会遗传变异标准与指南,c.839T>C(p.Leu280Pro)和c.239G>T(p.Arg80Leu)变异均判定为可能致病(PM2+PP1+PP2+PP3+PP4,PM2+PM5+PP1+PP2+PP3+PP4)。结论HSD17B3基因c.239G>T和c.839T>C复合杂合变异可能为该家系患儿的致病原因,17β-HSD3缺乏症临床表现及实验室检查缺乏特异性,基因检测结果可以为临床诊断提供依据。Objective To explore the genetic basis for a sib pair featuring 17β-hydroxysteroid dehydrogenase type 3 deficiency.Methods Genomic DNA was extracted from the proband,her sister,and their parents,and was subjected to sequencing analysis with a gene panel for sexual development.Suspected variant was verified by Sanger sequencing and bioinformatic analysis.Results Both the proband and her sister were found to harbor novel compound heterozygous missense variants of the HSD17B3 gene,namely c.839T>C(p.Leu280Pro)and c.239G>T(p.Arg80Leu),which were derived respectively from their mother and father.The variants were unreported previously and predicted to be deleterious by PolyPhen2,MutationTaster and other online software.Based on the American College of Medical Genetics and Genomics standards and guidelines,both c.839T>C(p.Leu280Pro)and c.239G>T(p.Arg80Leu)were predicted to be likely pathogenic(PM2+PP1+PP2+PP3+PP4,PM2+PM5+PP1+PP2+PP3+PP4).Conclusion The compound heterogeneous variants of the HSD17B3 gene probably underlay the disease in this sib pair.17β-hydroxysteroid dehydrogenase type 3 deficiency may lack specific clinical features and laboratory index,genetic testing can facilitate a definitive diagnosis.

关 键 词：HSD17B3基因 基因变异 17β-羟类固醇脱氢酶3型缺乏症 男性化不全 

分 类 号：R725.9[医药卫生—儿科]