Utility of whole exome sequencing in the evaluation of isolated fetal growth restriction in normal chromosomal microarray analysis

Objective To investigate the application of whole exome sequencing (WES) in the prenatal diagnosis of isolated fetal growth restriction (FGR) with a normal result by chromosomal microarray analysis (CMA).Methods This retrospective study included singleton fetuses with isolated FGR in Guangdong Women...

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Main Authors: Xiaomei Shi, Yanling Huang, Hongke Ding, Lina Zhao, Wei He, Jing Wu
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Annals of Medicine
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Online Access:https://www.tandfonline.com/doi/10.1080/07853890.2025.2476038
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author Xiaomei Shi
Yanling Huang
Hongke Ding
Lina Zhao
Wei He
Jing Wu
author_facet Xiaomei Shi
Yanling Huang
Hongke Ding
Lina Zhao
Wei He
Jing Wu
author_sort Xiaomei Shi
collection DOAJ
description Objective To investigate the application of whole exome sequencing (WES) in the prenatal diagnosis of isolated fetal growth restriction (FGR) with a normal result by chromosomal microarray analysis (CMA).Methods This retrospective study included singleton fetuses with isolated FGR in Guangdong Women and Children Hospital between July 2018 and August 2023. All fetuses were subjected to invasive prenatal testing with CMA and WES. Only cases with negative CMA results were included.Results r  A total of 135 fetuses were included. Ultrasonography identified short long bones in 39 fetuses and nonshort long bones in 96 cases. WES revealed pathogenic/likely pathogenic (P/LP) variants in 16(11.9%) fetuses and variants of uncertain significance (VUS) in 2 (1.5%) fetuses. Compared to the nonshort long bones group, the short long bones group had a significantly higher detection rate of P/LP variants (33.3% [13/39] vs. 3.1% [3/96], p < 0.001, OR=15.5(4.1-58.5)). No significant differences were observed in the detection rates between severe FGR and nonsevere FGR (12.3% [13/106] vs. 10.3% [3/29], p= .000, OR=1.2(0.3-4.6)), or between the early-onset (12.9% [15/116]) and the late-onset group (5.3%[1/19],p =0.565, OR=2.7(0.3-21.5)).Conclusions P/LP variants are more prevalent in fetuses with short long bones. WES is recommended for isolated FGR with short long bones, but further studies are needed to assess its utility in cases with nonshort long bones.
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spelling doaj-art-a1b4dff20fe740539d237d38b81e7b7b2025-08-20T03:21:39ZengTaylor & Francis GroupAnnals of Medicine0785-38901365-20602025-12-0157110.1080/07853890.2025.2476038Utility of whole exome sequencing in the evaluation of isolated fetal growth restriction in normal chromosomal microarray analysisXiaomei Shi0Yanling Huang1Hongke Ding2Lina Zhao3Wei He4Jing Wu5Genetic Medical Center, Guangdong Women and Children Hospital. Xingnan Load, Guangzhou, ChinaGenetic Medical Center, Guangdong Women and Children Hospital. Xingnan Load, Guangzhou, ChinaGenetic Medical Center, Guangdong Women and Children Hospital. Xingnan Load, Guangzhou, ChinaDepartment of Obstetrics, Guangdong Women and Children Hospital. Xingnan Load, Guangzhou, ChinaGenetic Medical Center, Guangdong Women and Children Hospital. Xingnan Load, Guangzhou, ChinaGenetic Medical Center, Guangdong Women and Children Hospital. Xingnan Load, Guangzhou, ChinaObjective To investigate the application of whole exome sequencing (WES) in the prenatal diagnosis of isolated fetal growth restriction (FGR) with a normal result by chromosomal microarray analysis (CMA).Methods This retrospective study included singleton fetuses with isolated FGR in Guangdong Women and Children Hospital between July 2018 and August 2023. All fetuses were subjected to invasive prenatal testing with CMA and WES. Only cases with negative CMA results were included.Results r  A total of 135 fetuses were included. Ultrasonography identified short long bones in 39 fetuses and nonshort long bones in 96 cases. WES revealed pathogenic/likely pathogenic (P/LP) variants in 16(11.9%) fetuses and variants of uncertain significance (VUS) in 2 (1.5%) fetuses. Compared to the nonshort long bones group, the short long bones group had a significantly higher detection rate of P/LP variants (33.3% [13/39] vs. 3.1% [3/96], p < 0.001, OR=15.5(4.1-58.5)). No significant differences were observed in the detection rates between severe FGR and nonsevere FGR (12.3% [13/106] vs. 10.3% [3/29], p= .000, OR=1.2(0.3-4.6)), or between the early-onset (12.9% [15/116]) and the late-onset group (5.3%[1/19],p =0.565, OR=2.7(0.3-21.5)).Conclusions P/LP variants are more prevalent in fetuses with short long bones. WES is recommended for isolated FGR with short long bones, but further studies are needed to assess its utility in cases with nonshort long bones.https://www.tandfonline.com/doi/10.1080/07853890.2025.2476038Whole exome sequencinggenetic abnormalitiesprenatal diagnosisFGR
spellingShingle Xiaomei Shi
Yanling Huang
Hongke Ding
Lina Zhao
Wei He
Jing Wu
Utility of whole exome sequencing in the evaluation of isolated fetal growth restriction in normal chromosomal microarray analysis
Annals of Medicine
Whole exome sequencing
genetic abnormalities
prenatal diagnosis
FGR
title Utility of whole exome sequencing in the evaluation of isolated fetal growth restriction in normal chromosomal microarray analysis
title_full Utility of whole exome sequencing in the evaluation of isolated fetal growth restriction in normal chromosomal microarray analysis
title_fullStr Utility of whole exome sequencing in the evaluation of isolated fetal growth restriction in normal chromosomal microarray analysis
title_full_unstemmed Utility of whole exome sequencing in the evaluation of isolated fetal growth restriction in normal chromosomal microarray analysis
title_short Utility of whole exome sequencing in the evaluation of isolated fetal growth restriction in normal chromosomal microarray analysis
title_sort utility of whole exome sequencing in the evaluation of isolated fetal growth restriction in normal chromosomal microarray analysis
topic Whole exome sequencing
genetic abnormalities
prenatal diagnosis
FGR
url https://www.tandfonline.com/doi/10.1080/07853890.2025.2476038
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