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.