摘要
目的探讨1例产前筛查高风险及超声提示心脏异常的胎儿的遗传学特征。方法选择2023年8月21日就诊于宁波大学附属妇女儿童医院的1例孕妇及其胎儿作为研究对象,回顾性分析其临床资料。采集孕妇的外周血样进行无创产前检测(NIPT),对其羊水细胞进行G显带染色体核型分析,对孕妇及配偶的外周血样和羊水样本进行全外显子组测序。针对拷贝数变异(CNV),对胎儿及父母的DNA进行实时荧光定量PCR(qPCR)验证。同时对夫妻双方进行外周血染色体核型分析。本研究通过了宁波大学附属妇女儿童医院医学伦理委员会的审查(EC2020-048)。结果孕22+6周超声检查提示胎儿宫内生长发育迟缓、室间隔缺损、主动脉骑跨、肺动脉细窄。NIPT检测提示胎儿13、18、21号染色体非整倍体为低风险。G显带分析提示胎儿核型为45,XY,-2[5]/46,XY,r(2)(p25q37)[55]。全外显子组测序分析提示胎儿染色体2p25.3区可能存在约1614.28 kb的杂合性缺失,结果为Seq[hg38]del(2)(p25.3p25.3)chr2:g.10500_1624775del。胎儿父母均未见异常,考虑为新发变异。qPCR检测显示胎儿样本中目的基因的表达量显著降低(P<0.05),其父母均未见明显异常。结论2号环状染色体可能为上述胎儿宫内生长发育迟缓及心血管畸形的遗传学病因。
Objective To explore the genetic basis for a fetus with increased risk for Down syndrome and cardiac anomalies discovered by prenatal ultrasonography.Methods A pregnant woman presented at the Women and Children′s Hospital of Ningbo University on August 21,2023 were selected as the study subject.Clinical data were retrospectively analyzed.Maternal peripheral blood sample was collected for non-invasive prenatal testing(NIPT)based on fetal free DNA.Amniotic fluid sample was collected for G-banded chromosomal karyotyping analysis.Trio-whole exome sequencing(WES)was also carried out on the amniotic fluid sample and peripheral blood samples from the couple.Copy number variation(CNV)identified by the WES was validated by real-time fluorescent quantitative PCR(qPCR).Chromosomal karyotyping was also carried out for the couple.This study has been approved by the Medical Ethics Committee of Women and Children′s Hospital of Ningbo University(No.EC2020-048).Results Ultrasound examination at 22+6 gestational weeks had indicated intrauterine growth retardation(IUGR).The fetus was also found to have ventricular septal defect,overriding aorta and pulmonary stenosis.NIPT indicated a low risk for aneuploidy of chromosomes 13,18 and 21.G-banding analysis revealed that the fetus had a karyotype of 45,XY,-2[5]/46,XY,r(2)(p25q37)[55].WES has identified a deletion of approximately 1614.28 kb in the 2p25.3 region,namely seq[hg38]del(2)(p25.3p25.3)chr2:g.10500_1624775del.The same deletion was found in neither parent,suggesting a de novo origin.qPCR results confirmed the expression of target genes in the fetal sample to be significantly reduced,whilst no similar anomaly was found in either parent.Conclusion The mosaicism ring chromosome 2 probably underlay the IUGR and cardiovascular malformations in this fetus.
作者
周颖
徐玲玲
闫露露
陈长水
李海波
Zhou Ying;Xu Lingling;Yan Lulu;Chen Changshui;Li Haibo(Central Laboratory for Birth Defects Prevention and Control,Women and Children′s Hospital of Ningbo University,Ningbo,Zhejiang 315012,China;Ningbo Key Laboratory for the Prevention and Treatment of Embryogenic Diseases,Women and Children′s Hospital of Ningbo University,Ningbo,Zhejiang 315012,China)
出处
《中华医学遗传学杂志》
CAS
CSCD
2024年第11期1356-1362,共7页
Chinese Journal of Medical Genetics
基金
宁波市社会公益重点项目(2022S035)
宁波市医疗卫生高端团队重大攻坚项目(2022020405)
宁波市"揭榜挂帅"重点研发计划(2023Z178)。
