Application of Prenatal Whole Exome Sequencing for Congenital Heart Anomalies
Issued Date
2026-02-01
Resource Type
ISSN
16616596
eISSN
14220067
Scopus ID
2-s2.0-105031376073
Journal Title
International Journal of Molecular Sciences
Volume
27
Issue
4
Rights Holder(s)
SCOPUS
Bibliographic Citation
International Journal of Molecular Sciences Vol.27 No.4 (2026)
Suggested Citation
Kamlungkuea T., Tongprasert F., Wattanasirichaigoon D., Kumfu S., Chattipakorn S.C., Chattipakorn N., Tongsong T. Application of Prenatal Whole Exome Sequencing for Congenital Heart Anomalies. International Journal of Molecular Sciences Vol.27 No.4 (2026). doi:10.3390/ijms27041720 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/115581
Title
Application of Prenatal Whole Exome Sequencing for Congenital Heart Anomalies
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Corresponding Author(s)
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Abstract
Congenital heart disease (CHD) is the most common congenital anomaly worldwide and poses significant diagnostic challenges due to its structural complexity and frequent association with extracardiac anomalies and genetic abnormalities. While conventional tests such as karyotyping, quantitative fluorescent polymerase chain reaction (QF-PCR), and chromosomal microarray analysis (CMA) are standard first-tier investigations, many cases remain genetically unexplained. Prenatal whole exome sequencing (WES) has emerged as a valuable tool to detect pathogenic single gene variants underlying CHD. This narrative review synthesizes findings from 28 studies involving over 2000 WES-tested fetuses and more than 10,000 CHD cases. The additional diagnostic yield of WES over CMA ranged from 8.0% to 66.7%, with higher yields in syndromic or non-isolated CHD (10–50%) compared to isolated cases (7.1–27.8%). Trio-based WES outperformed proband-only sequencing by improving accuracy, reducing turnaround time, and lowering the rate of variant of uncertain significance (VUS). Prenatal WES not only clarifies genetic etiology but also reveals syndromic diagnoses, allowing CHD to be interpreted within broader multisystem contexts. Integration of phenotypic and genomic data enhances prenatal counseling, prognostication, delivery planning, and postnatal care—advancing precision medicine in fetal cardiology.