全外显子组测序鉴定侏儒症家系基因突变及产前诊断  

Whole exome sequencing identifies gene mutations in a dwarfism family and prenatal diagnosis

作　　者：伊江燕 赵琼珍 张雪萍 张雪 杨钦涵 黄卫东 Yi Jiangyan;Zhao Qiongzhen;Zhang Xueping;Zhang Xue;Yang Qinhan;Huang Weidong(Department of Reproductive Medicine Center,Xinjiang JiaYin Hospital,Urumqi Xinjiang 830000,P.R.China)

机构地区：[1]新疆佳音医院生殖医学中心,新疆乌鲁木齐830000

出　　处：《中国计划生育和妇产科》2022年第10期45-48,I0003,共5页Chinese Journal of Family Planning & Gynecotokology

基　　金：新疆维吾尔自治区社会办医疗机构协会临床科研项目(项目编号:SHB202009)。

摘　　要：目的揭示一侏儒症患者家系的遗传病因,为遗传咨询和产前诊断提供有效信息。方法应用全外显子组测序(whole exome sequencing,WES)技术对侏儒症家系成员进行致病基因及突变位点筛查,结合临床表型,确定候选基因的致病位点,通过Sanger测序法对WES结果进行验证,排除二代测序假阳性位点。最后,利用鉴定得出的该家系致病基因的突变位点信息对患者胎儿进行产前诊断。结果WES结果显示先证者、先证者父亲、先证者胎儿均存在FGFR3基因NM_001163213.1:c.1626C>G(p.Asn542Lys)位点杂合变异,先证者妻子此未位点未发生突变。胎儿经超声检测股骨长度低于-2SD,有极大概率患有侏儒症。Sanger测序检测结果与上述WES结果一致,进一步证明了该检测结果的可靠性。结论FGFR3基因NM_001163213.1:c.1626C>G(p.Asn542Lys)位点杂合变异是侏儒症的重要发病原因,侏儒症患者3代的遗传咨询和产前诊断应重视该位点的检测。Objective To reveal the genetic etiology of a family of patients with dwarfism,and to provide effective information for genetic counseling and prenatal diagnosis.Methods Whole exome sequencing(WES)technology was used to screen the pathogenic genes and mutation sites of dwarfism family members,and the pathogenic sites of candidate genes were determined by combining clinical phenotypes.The WES results were verified by Sanger sequencing to exclude false positive sites by next-generation sequencing.Finally,prenatal diagnosis of the patient’s fetus was carried out using the identified mutation site information of the causative gene in this family.Results The results of WES showed that the proband,the father of the proband,and the fetus of the proband all had the FGFR3 gene NM_001163213.1:c.1626 C>G(p.Asn542 Lys)heterozygous variant,but the wife of the proband did not have this locus.Fetuses with a femoral length less than-2 SD detected by ultrasound had a high probability of dwarfism.The Sanger sequencing test results were consistent with the above WES results,further proving the reliability of the test results.Conclusion Heterozygous variant of FGFR3 gene NM_001163213.1:c.1626 C>G(p.Asn542 Lys)locus is an important cause of dwarfism.Genetic counseling and prenatal diagnosis of offspring of patients with dwarfism should pay attention to the detection of this locus.

关 键 词：侏儒症 FGFR3基因 产前诊断 基因突变 

分 类 号：R394.1[医药卫生—医学遗传学]