• Clinical significance of regio...

Treffer: Clinical significance of regions of homozygosity detection in prenatal chromosomal microarray analysis.

Title:
Clinical significance of regions of homozygosity detection in prenatal chromosomal microarray analysis.
Authors:
Hao Y; Medical Genetic Center, Shenzhen Maternity and Child Healthcare Hospital, Women and Children's Medical Center, Southern Medical University, Shenzhen, China., Geng Q; Medical Genetic Center, Shenzhen Maternity and Child Healthcare Hospital, Women and Children's Medical Center, Southern Medical University, Shenzhen, China., Li X; Medical Genetic Center, Shenzhen Maternity and Child Healthcare Hospital, Women and Children's Medical Center, Southern Medical University, Shenzhen, China., Yang J; Medical Genetic Center, Shenzhen Maternity and Child Healthcare Hospital, Women and Children's Medical Center, Southern Medical University, Shenzhen, China., Liu Y; Medical Genetic Center, Shenzhen Maternity and Child Healthcare Hospital, Women and Children's Medical Center, Southern Medical University, Shenzhen, China., Huang Q; Medical Genetic Center, Shenzhen Maternity and Child Healthcare Hospital, Women and Children's Medical Center, Southern Medical University, Shenzhen, China., Xu Y; Medical Genetic Center, Shenzhen Maternity and Child Healthcare Hospital, Women and Children's Medical Center, Southern Medical University, Shenzhen, China., Li P; Department of Genetics, Yale University School of Medicine, New Haven, CT, USA., Xie J; Medical Genetic Center, Shenzhen Maternity and Child Healthcare Hospital, Women and Children's Medical Center, Southern Medical University, Shenzhen, China; Reproductive Medicine and Prenatal Diagnosis Center, Division of Prenatal Diagnosis, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China., Wu W; Medical Genetic Center, Shenzhen Maternity and Child Healthcare Hospital, Women and Children's Medical Center, Southern Medical University, Shenzhen, China., Wu B; Medical Genetic Center, Shenzhen Maternity and Child Healthcare Hospital, Women and Children's Medical Center, Southern Medical University, Shenzhen, China; Shenzhen Key Laboratory of Maternal and Child Health and Diseases, Shenzhen, China. Electronic address: wubo@szmch.net.cn., Liu W; Medical Genetic Center, Shenzhen Maternity and Child Healthcare Hospital, Women and Children's Medical Center, Southern Medical University, Shenzhen, China; Shenzhen Key Laboratory of Maternal and Child Health and Diseases, Shenzhen, China. Electronic address: lwl@szmch.net.cn.
Source:
HGG advances [HGG Adv] 2026 Jan 15; Vol. 7 (1), pp. 100549. Date of Electronic Publication: 2025 Nov 19.
Publication Type:
Journal Article
Language:
English
Journal Info:
Publisher: Elsevier Inc Country of Publication: United States NLM ID: 101772885 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2666-2477 (Electronic) Linking ISSN: 26662477 NLM ISO Abbreviation: HGG Adv Subsets: MEDLINE
Imprint Name(s):
Original Publication: New York : Elsevier Inc., [2020]-
MeSH Terms:
Prenatal Diagnosis*/methods , Homozygote* , Microarray Analysis*/methods, Humans ; Female ; Pregnancy ; DNA Copy Number Variations ; Genetic Testing/methods ; Adult ; Exome Sequencing ; Uniparental Disomy/genetics ; Uniparental Disomy/diagnosis ; Clinical Relevance
Contributed Indexing:
Keywords: chromosome microarray analysis; copy-number variant; exome sequencing; prenatal diagnosis; regions of homozygosity; uniparental disomy
Entry Date(s):
Date Created: 20251121 Date Completed: 20260116 Latest Revision: 20260116
Update Code:
20260117
DOI:
10.1016/j.xhgg.2025.100549
PMID:
41267400
Database:
MEDLINE

Weitere Informationen

Chromosomal microarray analysis (CMA) detects pathogenic copy-number variants (pCNVs) and regions of homozygosity (ROHs) in prenatal genetic analysis. This study evaluates the clinical significance of ROH detection in prenatal settings. We reviewed 178 fetuses with ROH detected by CMA among 20,546 fetuses from 2015 to 2023. Clinical and laboratory results, including ultrasound anomalies, cell-free DNA (cfDNA) screening, karyotyping, exome sequencing (ES), and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA), were analyzed. These 178 fetuses with ROH accounted for 0.87% of prenatal cases. Among them, 24.2% had positive cfDNA screening results, and 52.8% underwent follow-up ES, trio CMA, and MS-MLPA. Follow-up studies detected pathogenic homozygous variants within ROH in two fetuses and uniparental disomy (UPD)-related diseases in five fetuses. Our results and findings from the other five large prenatal case series from literature indicated that ROH detection in prenatal CMA has a baseline positive predictive value of 2.7% for autosomal-recessive disorders, 9.6% for UPD-related diseases, and 0.04% overall additive diagnostic yield. These findings support the use of ES and MS-MLPA for follow-up testing and provide guidance for genetic counseling in fetuses with ROH.
(Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Declaration of interests The authors declare no competing interests.