Mol Cytogenet. 2025 Dec 4. doi: 10.1186/s13039-025-00741-4. Online ahead of print.
ABSTRACT
BACKGROUND: Copy number variations (CNVs) of uncertain significance (VUS) are increasingly identified through prenatal and postnatal genetic testing, yet their clinical interpretation remains challenging. We report a neonate with hematologic and genitourinary anomalies in whom a de novo duplication at chromosome 2q23.1-2q23.3 was discovered, prompting further genomic and clinical investigation.
MAIN BODY: The patient was born via cesarean section due to oligohydramnios and increased umbilical artery flow, following an otherwise normal pregnancy. Postnatal findings included anemia, thrombocytopenia, and hypospadias. Genetic analysis revealed a 1.5 Mb duplication at 2q23.1-2q23.3 (chr2:149,390,001-150,890,000, GRCh37), encompassing several protein-coding genes. Parental testing confirmed the duplication was de novo. The CNV overlaps with regions previously associated with 2q23.1 microduplication syndrome, although the phenotype in this case differs. A separate 1.02 Mb duplication at 3p26.3 was identified in the father, involving the CHL1 gene, but was not inherited and is not considered contributory. The 2q23.2 duplication was not found in population CNV databases including gnomAD-SV, DGV, and ClinGen, suggesting it is rare or novel. A detailed clinical summary and genomic analysis were performed to explore genotype-phenotype correlations.
CONCLUSION: This case underscores the importance of integrating clinical and genomic data to interpret de novo CNVs in neonates. The findings contribute to the understanding of rare duplications in the 2q23 region and highlight the need for cautious interpretation of incidental parental variants. Further studies are needed to elucidate the pathogenic potential of such duplications and their role in neonatal disease.
PMID:41345686 | DOI:10.1186/s13039-025-00741-4
