TY - JOUR

T1 - Whole Genome Sequencing in the Evaluation of Fetal Structural Anomalies

T2 - A Parallel Test with Chromosomal Microarray Plus Whole Exome Sequencing

AU - Zhou, Jia

AU - Yang, Ziying

AU - Sun, Jun

AU - Liu, Lipei

AU - Zhou, Xinyao

AU - Liu, Fengxia

AU - Xing, Ya

AU - Cui, Shuge

AU - Xiong, Shiyi

AU - Liu, Xiaoyu

AU - Yang, Yingjun

AU - Wei, Xiuxiu

AU - Zou, Gang

AU - Wang, Zhonghua

AU - Wei, Xing

AU - Wang, Yaoshen

AU - Zhang, Yun

AU - Yan, Saiying

AU - Wu, Fengyu

AU - Zeng, Fanwei

AU - Wang, Jian

AU - Duan, Tao

AU - Peng, Zhiyu

AU - Sun, Luming

PY - 2021

Y1 - 2021

N2 - Whole genome sequencing (WGS) is a powerful tool for postnatal genetic diagnosis, but relevant clinical studies in the field of prenatal diagnosis are limited. The present study aimed to prospectively evaluate the utility of WGS compared with chromosomal microarray (CMA) and whole exome sequencing (WES) in the prenatal diagnosis of fetal structural anomalies. We performed trio WGS (≈40-fold) in parallel with CMA in 111 fetuses with structural or growth anomalies, and sequentially performed WES when CMA was negative (CMA plus WES). In comparison, WGS not only detected all pathogenic genetic variants in 22 diagnosed cases identified by CMA plus WES, yielding a diagnostic rate of 19.8% (22/110), but also provided additional and clinically significant information, including a case of balanced translocations and a case of intrauterine infection, which might not be detectable by CMA or WES. WGS also required less DNA (100 ng) as input and could provide a rapid turnaround time (TAT, 18 ± 6 days) compared with that (31 ± 8 days) of the CMA plus WES. Our results showed that WGS provided more comprehensive and precise genetic information with a rapid TAT and less DNA required than CMA plus WES, which enables it as an alternative prenatal diagnosis test for fetal structural anomalies.

AB - Whole genome sequencing (WGS) is a powerful tool for postnatal genetic diagnosis, but relevant clinical studies in the field of prenatal diagnosis are limited. The present study aimed to prospectively evaluate the utility of WGS compared with chromosomal microarray (CMA) and whole exome sequencing (WES) in the prenatal diagnosis of fetal structural anomalies. We performed trio WGS (≈40-fold) in parallel with CMA in 111 fetuses with structural or growth anomalies, and sequentially performed WES when CMA was negative (CMA plus WES). In comparison, WGS not only detected all pathogenic genetic variants in 22 diagnosed cases identified by CMA plus WES, yielding a diagnostic rate of 19.8% (22/110), but also provided additional and clinically significant information, including a case of balanced translocations and a case of intrauterine infection, which might not be detectable by CMA or WES. WGS also required less DNA (100 ng) as input and could provide a rapid turnaround time (TAT, 18 ± 6 days) compared with that (31 ± 8 days) of the CMA plus WES. Our results showed that WGS provided more comprehensive and precise genetic information with a rapid TAT and less DNA required than CMA plus WES, which enables it as an alternative prenatal diagnosis test for fetal structural anomalies.

KW - Chromosomal microarray

KW - Fetal structural anomalies

KW - Prenatal diagnosis

KW - Whole exome sequencing

KW - Whole genome sequencing

U2 - 10.3390/genes12030376

DO - 10.3390/genes12030376

M3 - Journal article

C2 - 33800913

AN - SCOPUS:85102860227

VL - 12

JO - Genes

JF - Genes

SN - 2073-4425

IS - 3

M1 - 376

ER -