Whole-exome sequencing reveals genetic etiology and pregnancy outcomes in fetuses with ultrasound-detected abnormalities at a tertiary center.
- 1Fujian Key Laboratory for Prenatal Diagnosis and Birth Defect, Medical Genetic Diagnosis and Therapy Center, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, China.
Abstract
Despite advances in prenatal diagnostics, the genetic causes underlying fetal ultrasound abnormalities remain poorly understood, with a significant proportion of cases lacking definitive molecular diagnoses. Invasive prenatal testing was performed in 179 cases, followed by whole-exome sequencing (WES) to identify genetic etiologies. Among 179 abnormal fetuses, 132 had single-system and 47 had multisystem abnormalities. WES identified pathogenic (P) or likely pathogenic (LP) variants in 33 cases (19 single-system, 14 multisystem), with skeletal (7), cardiac (5), and craniofacial defects (2) being most frequent. Thirty-four genes were involved, encompassing 41 variants (15 missense, 10 frameshift, 6 splicing, 6 nonsense, and 4 in-frame deletions). WES yielded a P/LP rate of 17.88% (32/179) for variants that explained the fetal phenotype, with an additional pathogenic finding (overall P/LP rate: 18.44%, 33/179). Inheritance patterns were autosomal dominant (19), recessive (12), X-linked (1), and mosaic (1). Family studies confirmed 27 variants (18 inherited, 9 de novo). Pregnancy outcomes included 60 terminations, 19 intrauterine deaths, and 8 postnatal abnormalities. Most fetal ultrasound phenotypes matched the disease-causing gene profiles. Combining molecular testing with ultrasound helps clinicians identify genetic causes, assess recurrence risk, and inform parents, enabling personalized management for high-risk families.
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BibTeX
@article{cai2026wholeexome,
title = {{Whole-exome sequencing reveals genetic etiology and pregnancy outcomes in fetuses with ultrasound-detected abnormalities at a tertiary center.}},
author = {Meiying Cai and Na Lin and Hailong Huang and Meimei Fu and Yifang Dai and Liangpu Xu},
journal = {Frontiers in genetics},
year = {2026},
month = oct,
doi = {10.3389/fgene.2026.1858421},
url = {https://europepmc.org/article/MED/42936866},
note = {CC BY},
}
RIS
TY - JOUR
TI - Whole-exome sequencing reveals genetic etiology and pregnancy outcomes in fetuses with ultrasound-detected abnormalities at a tertiary center.
AU - Meiying Cai
AU - Na Lin
AU - Hailong Huang
AU - Meimei Fu
AU - Yifang Dai
AU - Liangpu Xu
PY - 2026
DA - 2026/10/13
JO - Frontiers in genetics
DO - 10.3389/fgene.2026.1858421
UR - https://europepmc.org/article/MED/42936866
AB - Despite advances in prenatal diagnostics, the genetic causes underlying fetal ultrasound abnormalities remain poorly understood, with a significant proportion of cases lacking definitive molecular diagnoses. Invasive prenatal testing was performed in 179 cases, followed by whole-exome sequencing (WES) to identify genetic etiologies. Among 179 abnormal fetuses, 132 had single-system and 47 had multisystem abnormalities. WES identified pathogenic (P) or likely pathogenic (LP) variants in 33 cases (19 single-system, 14 multisystem), with skeletal (7), cardiac (5), and craniofacial defects (2) being most frequent. Thirty-four genes were involved, encompassing 41 variants (15 missense, 10 frameshift, 6 splicing, 6 nonsense, and 4 in-frame deletions). WES yielded a P/LP rate of 17.88% (32/179) for variants that explained the fetal phenotype, with an additional pathogenic finding (overall P/LP rate: 18.44%, 33/179). Inheritance patterns were autosomal dominant (19), recessive (12), X-linked (1), and mosaic (1). Family studies confirmed 27 variants (18 inherited, 9 de novo). Pregnancy outcomes included 60 terminations, 19 intrauterine deaths, and 8 postnatal abnormalities. Most fetal ultrasound phenotypes matched the disease-causing gene profiles. Combining molecular testing with ultrasound helps clinicians identify genetic causes, assess recurrence risk, and inform parents, enabling personalized management for high-risk families.
SN - 1664-8021
ER -