Analysis of families with fetal congenital abnormalities but negative prenatal diagnosis by whole exome sequencing
10.3760/cma.j.cn112141-20210118-00028
- VernacularTitle:对传统产前诊断阴性的先天性发育异常胎儿家系应用全外显子测序技术的分析
- Author:
Fang FU
1
;
Lushan LI
;
Kun DU
;
Ru LI
;
Qiuxia YU
;
Dan WANG
;
Tingying LEI
;
Qiong DENG
;
Zhiqiang NIE
;
Wenwen ZHANG
;
Xin YANG
;
Jin HAN
;
Li ZHEN
;
Min PAN
;
Lina ZHANG
;
Fucheng LI
;
Yongling ZHANG
;
Xiangyi JING
;
Dongzhi LI
;
Can LIAO
Author Information
1. 广州医科大学附属广州市妇女儿童医疗中心产前诊断中心 510623
- Keywords:
Whole exome sequencing;
Congenital abnormalities;
Prenatal diagnosis;
Pedigree;
Reproducibility of results
- From:
Chinese Journal of Obstetrics and Gynecology
2021;56(7):458-466
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To evaluate the value of whole exome sequencing (WES) in prenatal clinical application.Methods:A total of 1 152 cases of congenital abnormal [including structural malformation, nuchal translucency (NT) thickening and intrauterine growth restriction] with traditional prenatal diagnosis [including G-band karyotype analysis and chromosome microarray analysis (CMA)] negative were analyzed. The congenital abnormal fetuses were divided into retrospective group and prospective group according to the time of WES detection, that is whether the pregnancy termination or not. According to the specific location of fetal malformation and their family history, the cohort was divided into subgroups. The clinical prognosis of all fetuses were followed up, and the effect of WES test results on pregnancy decision-making and clinical intervention were analyzed. According to the follow-up results, the data of fetuses with new phenotypes in the third trimester or after birth were re-analyzed.Results:Among 1 152 families who received WES, 5 families were excluded because of nonbiological parents. Among the remaining 1 147 families, 152 fetuses obtained positive diagnosis (13.3%,152/1 147), including 74 fetuses in the retrospective group (16.1%,74/460) and 78 fetuses in the prospective group (11.4%,78/687). In fetuses with negative CMA and G-band karyotype analysis results but new phenotypes in the third trimester or after birth, the positive rate by WES data re-analysis was 4.9% (8/163). A total of 34 (21.3%, 34/160) fetuses were directly affected by the corresponding positive molecular diagnosis. Among 68 cases of live births with diagnostic variation grade 4, 29 cases (42.7%, 29/68) received appropriate medical intervention through rapid review of WES results.Conclusions:WES could increase the detection rate of abnormal fetuses with negative G-banding karyotype analysis and CMA by 13.3%. Prenatal WES could guide pregnancy decision-making and early clinical intervention. It might be an effective strategy to pay attention to the special follow-up of the third trimester and postnatal fetus and to re-analyze the WES data.
