Prenatal whole-exome sequencing for fetal structural anomalies: a retrospective analysis of 145 Chinese cases

BMC Medical Genomics

Research

Fanglian Zhang¹  Nian Liu²  Yanyi Yao²  Lijun Liu²  Tangxinzi Gao²  Bo Wang²  Yayun Qin²  Runhong Xu²  Xiaoyan Wang²  Jieping Song²  Hui Li² 

[1] Honghu Hospital of Traditional Chinese Medicine, 433200, Jingzhou, Hubei Province, China;Medical Genetics Center, Maternal and Child Health Hospital of Hubei Province, 430070, Wuhan, Hubei Province, China;

关键词: Whole-exome sequencing;    Prenatal diagnosis;    Structural anomalies;    Prenatal ultrasonography;   

DOI  :  10.1186/s12920-023-01697-3

 received in 2023-03-23, accepted in 2023-10-12,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundWhole-exome sequencing (WES) significantly improves the diagnosis of the etiology of fetal structural anomalies. This study aims to evaluate the diagnostic value of prenatal WES and to investigate the pathogenic variants in structurally abnormal fetuses.MethodsWe recruited 144 fetuses with structural anomalies between 14 and 2020 and 15 December 2021 in the study. Genetic screening was performed by WES combined with karyotyping and chromosomal microarray analysis. The molecular diagnostic yield of prenatal WES for each type of fetal structural anomaly and the identified pathogenic genes and mutations were reported.ResultsIn this study, we retrospectively analyzed the clinical and genetic data of 145 structurally anomalous fetuses. These cases were classified into 9 phenotypic classes based on antenatal ultrasound findings. Thirty-eight pathogenic variants in 24 genes were identified in 35 of the 145 cases, including 14 novel variants in 13 genes (EP300, MYH3, TSC2, MMP9, CPLANE1, INVS, COL1A1, EYA1, TTC21B, MKS1, COL11A2, PDHA1 and L1CAM). Five additional pathogenic variants were classified as incidental findings. Our study showed that the overall diagnosis rate of WES was 28.1% (27/96) in the parent-fetus trio cases and 16.3% (8/49) in the proband-only cases. Fetuses with musculoskeletal anomalies had the highest diagnostic yield (51.4%, 19/37). In addition, FGFR3 and COL1A1 were the most common pathogenic genes.ConclusionsOur work expands the mutation spectrum of the genes associated with fetal structural anomalies and provides valuable information for future parental genetic counselling and pregnancy management of the structurally anomalous fetuses.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

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