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Published: 2026-03-31
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DOI: https://doi.org/10.52852/tcncyh.v200i3.4770
Issue
Vol. 200 No. 3 (2026)
Section
Các bài báo
How to Cite
Hoa, B. T. P., Hùng, N. T., & Tú, N. N. (2026). Added diagnostic value of trio whole-genome sequencing in prenatally detected fetal anomalies with negative CMA and WES: Two case reports. Journal of Medical Research, 200(3), 612-619. https://doi.org/10.52852/tcncyh.v200i3.4770

Added diagnostic value of trio whole-genome sequencing in prenatally detected fetal anomalies with negative CMA and WES: Two case reports

Bui Thi Phuong Hoa, Nguyen The Hung, Nguyen Ngoc Tu

Main Article Content

Abstract

This report presents two clinical cases that illustrate the added diagnostic value of WGS when prior tests are negative. Case 1: A male fetus with recurrent familial hydrocephalus. WGS detected a hemizygous deletion involving exon 6 and part of exon 7 of L1CAM, classified as likely pathogenic and consistent with X-linked L1 syndrome. The mother was identified as a carrier, recurrence-risk counselling was modified accordingly and PGT-M planning were provided. Case 2: A fetus with multiple cerebral malformations. Trio-WGS revealed a heterozygous de novo deletion of CREBBP (exons 29–31), classified as pathogenic and compatible with Rubinstein–Taybi syndrome. Based on the test result, the prognosis was refined and would greatly reduced the estimated recurrence risk for future pregnancies. WGS expands the detectable spectrum of genetic variants, including SNVs/indels outside exonic regions, small CNVs, complex structural variants, ROH/UPD, and partial mitochondrial or low-level mosaic abnormalities, thereby providing diagnostic value and clinical impact after negative karyotype, CMA, and WES results.

Article Details

Keywords

Whole-genome sequencing, trio-WGS, prenatal abnormalities, L1CAM, CREBBP, CMA negative results, WES negative results, prenatal

References

1. Mellis R OK SE, Hill M, Chitty LS, et al. Diagnostic yield of exome sequencing for prenatal diagnosis of fetal structural anomalies: A systematic review and meta-analysis. Prenatal diagnosis 2022; 42(6): 662-685.
2. Callaway JL, Shaffer L G, Chitty L S, et al. The clinical utility of microarray technologies applied to prenatal cytogenetics in the presence of a normal conventional karyotype: a review of the literature. Prenatal diagnosis. 2013; 33(12): 1119-1123.
3. Liu X, Liu S, Wang H, et al. Potentials and challenges of chromosomal microarray analysis in prenatal diagnosis. Frontiers in genetics. 2022; 13:938183.
4. Best S, Wou K, Vora N, et al. Promises, pitfalls and practicalities of prenatal whole exome sequencing. Prenatal diagnosis. 2018; 38(1): 10-19.
5. Basel-Salmon L, Brabbing-Goldstein D. Fetal whole genome sequencing as a clinical diagnostic tool: Advantages, limitations and pitfalls Best Practice & Research Clinical Obstetrics & Gynaecology. 2024; 97: 102549.
6. Stumpel C VY. L1 Syndrome Vol 1993-2025: Seattle (WA): University of Washington, Seattle; 2004.
7. Babadi M, Fu J M, Lee S K, et al. GATK-gCNV enables the discovery of rare copy number variants from exome sequencing data. Nature genetics 2023; 55(9): 1589-1597.
8. Marchuk DS CK, Strande N, et al,. Increasing the diagnostic yield of exome sequencing by copy number variant analysis. PLoS One. 2018; 13(12): e0209185.
9. Thomas W Laver EDF, Matthew B Johnson, et al. Supervised exercise (Vivifrail) protects institutionalized older adults against severe functional decline after 14 weeks of COVID confinement. Journal of the American Medical Directors Association. 2021; 22(1): 217-219.