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

Abstract

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.