全外显子测序技术对胎儿颈部水囊瘤产前超声初筛患者再诊断的探讨  

Investigation of whole-exome sequencing technique for re-diagnosis of fetal neck cystic hygroma in patients with initial prenatal ultrasound screening

作　　者：安莉娜 马辉芳 李桢 田乐 潘丽华[1] AN Lina;MA Huifang;LI Zhen;TIAN Le;PAN Lihua(Prenatal Diagnosis Center,General Hospital of Ningxia Medical University,Yinchuan 750004,China)

机构地区：[1]宁夏医科大学总医院产前诊断中心,宁夏银川750004

出　　处：《宁夏医学杂志》2025年第3期194-198,F0002,共6页Ningxia Medical Journal

基　　金：宁夏重点研发计划项目(2023BEG02006)。

摘　　要：目的探讨全外显子测序技术(WES)对产前超声初筛胎儿颈部水囊瘤(CCH)再诊断的研究。方法回顾性收集在产前超声时发现胎儿颈部水囊瘤(CCH),进行介入性产前诊断的18例孕妇资料,按照超声指标将其分为超声结构异常和超声非结构异常2组,18例胎儿全部行染色体拷贝数变异检测(CNV-seq),并进行全外显子测序。结果本研究共纳入产前超声初筛发现的胎儿颈部水囊瘤共18例,不合并超声异常WES检出率为33.33%,合并超声异常WES检出率为66.67%;其中合并超声异常按照产前超声指标分为2组,合并超声结构异常胎儿有9例,WES检出率为50.0%,包括水肿胎和心脏异常各3例、骨骼异常1例、脑积水1例、多发畸形1例,合并超声非结构异常胎儿3例,WES检出率为16.67%。WES检出单基因变异共12例,占比为66.67%,与合并超声异常的检出率一致,18例胎儿中足月分娩的有2例、失访有1例、引产有15例,终止妊娠率为83.33%。检出常见单基因PTPN11、LZTR1、RAF1共3例,占比为16.67%,检出CCH罕见的基因包括CBL、GBE1、ARIDIA、RYR1、MYH3、GALE、MYH3、GALE、MYH2。本研究验证了1例CNV-seq阳性(21-三体综合征)的病例,WES额外检出CBL基因c.2037-7C>T杂合变异。结论WES对CCH合并其他超声异常检出率高于不合并其他超声异常的检出率;CCH与单基因遗传病和遗传综合征相关。Objective To explore the application of whole-exome sequencing(WES)in the re-diagnosis of fetal cystic hygroma(CCH)initially screened by prenatal ultrasound.Methods The data of 18 pregnant women with CCH detected by prenatal ultrasound and undergoing invasive prenatal diagnosis were retrospectively collected.The patients were divided into two groups according to ultrasound indicators:structural and non-structural abnormalities.All of 18 fetuses underwent chromosomal copy number variation detection(CNV-seq)and further WES.Results A total of 18 cases of fetal cervical hydatid cystic aneurysms on initial prenatal ultrasound screening were included in this study,the detection rate of WES without combined ultrasound abnormality was 33.33%,and the detection rate of WES with combined ultrasound abnormality was 66.67%.The detection rate of WES was 50.0%in 9 cases of fetuses with structural ultrasound abnormalities,including 3 cases of hydatidiform fetuses and 3 cases of cardiac anomalies,1 case of skeletal anomalies,1 case of hydrocephalus,1 case of multiple malformations,and 3 cases of fetuses with nonstructural ultrasound abnormalities,with a detection rate of WES of 16.67%.There were 12 cases of single gene variants detected by WES,accounting for 66.67%of the total,which was consistent with the detection rate of combined ultrasound anomalies.Among the 18 cases of fetuses,there were 2 cases of full-term deliveries,1 case of loss of pregnancy,and 15 cases of induced abortion,resulting in a termination of pregnancy rate of 83.33%.Common single genes PTPN11,LZTR1 and RAF1 were detected in 3 cases,auountins for 16.67%,and rare genes of CCH were detected,including CBL,GBE1,ARIDIA,RYR1,MYH3,GALE,MYH3,GALE,and MYH2.In the present study,one CNV-seq positive(trisomy 21)case was verified.WES additionally detected a heterozygous variant of the CBL gene c.2037-7C>T.Conclusion The detection rate of WES in CCH with other ultrasound abnormalities is higher than that without other ultrasound abnormalities.CCH is associated with single

关 键 词：胎儿颈部水囊瘤 超声 全外显子测序技术 产前诊断 

分 类 号：R711[医药卫生—妇产科学]