A fetus with paternal uniparental isodisomy of chromosome 3: genetic analysis and prenatal diagnosis following a positive NIPS with IUGR.

IF 1.4 4区生物学 Q4 GENETICS & HEREDITY

Molecular Cytogenetics Pub Date : 2026-06-15 DOI:10.1186/s13039-026-00773-4

Fang Zhang, ShanShan Ma, Yongan Wang, Shuai Men, Rong Zhang, Ting Yin

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引用次数: 0

Abstract

Objective: To report a rare prenatal case of paternal uniparental isodisomy of chromosome 3 (upd(3)pat) associated with isolated intrauterine growth restriction (IUGR).

Methods: Expanded non‑invasive prenatal screening (NIPS) in a 19‑year‑old woman indicated a duplication on chromosome 3q. Amniocentesis was performed for karyotyping, chromosomal microarray analysis (CMA), and trio whole‑exome sequencing (WES). Copy number variation sequencing (CNV-seq) was performed for the validation of the placental tissue postpartum.

Results: Karyotype was normal (46,XY). CMA revealed a whole-chromosome region of homozygosity (ROH) on chromosome 3, and WES confirmed upd(3)pat with no recessive pathogenic variants. Third‑trimester ultrasound showed IUGR. A male infant weighing 2,450 g was delivered at 38 weeks with normal birth examination. CNV-seq confirmed trisomy 3 on the fetal side of the placenta. Follow-up assessment at 2.5 years of age showed unremarkable neurodevelopmental outcomes.

Conclusion: NIPS is a screening rather than a diagnostic test and all positive findings must be confirmed by invasive diagnostic procedures. Trisomy rescue can lead to coexistence of UPD3 with confined placental mosaicism (CPM). A multimodal approach incorporating karyotyping, CMA, trio‑WES, and CNV‑seq is essential for resolving discordant findings. This study expands the limited prenatal literature on upd(3)pat and highlights the critical importance of comprehensive genetic testing for accurate diagnosis and genetic counseling.

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3号染色体孤本同染色体胎儿：IUGR阳性NIPS后的遗传分析和产前诊断。

目的：报道一例罕见的与孤立性宫内生长受限（IUGR）相关的3号染色体父本单代同型二体（upd(3)pat）。方法：对一名19岁女性进行非侵入性产前筛查（NIPS），发现3q染色体存在重复。进行羊膜穿刺术进行核型分析、染色体微阵列分析（CMA）和三组全外显子组测序（WES）。采用拷贝数变异测序（CNV-seq）对产后胎盘组织进行验证。结果：核型正常（46，XY）。CMA在3号染色体上发现了一个全染色体纯合区（ROH）， WES证实了upd(3)部分，无隐性致病变异。妊娠晚期超声显示IUGR。在正常分娩检查下，孕38周分娩一名体重2450克的男婴。CNV-seq证实胎盘胎儿侧有3型三体。2.5岁时的随访评估显示神经发育结果不显著。结论：NIPS是一种筛查而非诊断试验，所有阳性结果必须通过侵入性诊断程序确认。三体抢救可导致UPD3与受限胎盘嵌合体（CPM）共存。结合核型、CMA、trio - WES和CNV - seq的多模式方法对于解决不一致的发现至关重要。本研究扩展了有限的产前文献upd(3)部分，并强调了全面的基因检测对准确诊断和遗传咨询的至关重要性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Cytogenetics GENETICS & HEREDITY-

CiteScore

2.60

自引率

7.70%

发文量

审稿时长

>12 weeks

期刊介绍： Molecular Cytogenetics encompasses all aspects of chromosome biology and the application of molecular cytogenetic techniques in all areas of biology and medicine, including structural and functional organization of the chromosome and nucleus, genome variation, expression and evolution, chromosome abnormalities and genomic variations in medical genetics and tumor genetics. Molecular Cytogenetics primarily defines a large set of the techniques that operate either with the entire genome or with specific targeted DNA sequences. Topical areas include, but are not limited to: -Structural and functional organization of chromosome and nucleus- Genome variation, expression and evolution- Animal and plant molecular cytogenetics and genomics- Chromosome abnormalities and genomic variations in clinical genetics- Applications in preimplantation, pre- and post-natal diagnosis- Applications in the central nervous system, cancer and haematology research- Previously unreported applications of molecular cytogenetic techniques- Development of new techniques or significant enhancements to established techniques. This journal is a source for numerous scientists all over the world, who wish to improve or introduce molecular cytogenetic techniques into their practice.