Maternal mixed UPD3 and a homozygous PLXNA1 c.2497G>C variant in a fetus with severe anomalies

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Source: Frontiers Medicine

Original: https://www.frontiersin.org/articles/10.3389/fmed.2025.1712148...

Published: 2026-01-23T00:00:00Z

The case describes a fetus with severe developmental anomalies whose non-invasive prenatal testing (NIPT) indicated a high risk of trisomy 3, with a Z-score of 27.22[1]. A more detailed genetic investigation using chromosomal microarray analysis (trio-CMA) ruled out trisomy 3 but confirmed mixed maternal uniparental disomy of chromosome 3 (UPD3), a rare genetic disorder[1]. Whole genome sequencing (trio-WGS) identified a homozygous variant in the PLXNA1 gene (c.2497G>C) in the fetus, which he inherited from the mother, who was a carrier of the heterozygous variant[1]. This PLXNA1 variant is associated with a putative autosomal recessive disorder and may represent a potential pathogenic cause of the observed severe fetal phenotype[1]. The authors propose a model in which an error in the division of chromosome 3 during germ cell formation led to a trisomy that subsequently self-corrected, resulting in mixed UPD3 and an increased risk of autosomal recessive disorders[1]. The case highlights that while NIPT may signal a high risk of rare aneuploidies, definitive diagnosis requires invasive prenatal testing[1].