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. 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. 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.

Background/Objectives: Miscarriage is an increasingly common event worldwide arising from various factors, and identifying its etiology is important for planning and managing any future pregnancies. It is estimated that about half of early pregnancy loss cases are caused by genetic abnormalities, while a significantly lower rate is found in late pregnancy loss. Multiplex ligation-dependent probe amplification (MLPA) can detect small changes within a gene with precise breakpoints at the level of a single exon. The aim of our study was to identify the rate of copy number variations (CNVs) in spontaneous pregnancy loss samples after having previously tested them via quantitative fluorescence PCR (QF-PCR), with no abnormal findings. Methods: DNA was extracted from product-of-conception tissue samples, followed by the use of an MLPA kit for the detection of 31 microdeletion/microduplication syndromes (SALSA® MLPA® Probemix P245 Microdeletion Syndromes-1A, MRC-Holland, Amsterdam, The Netherlands). Results: A total of 11 (13.1%) out of the 84 successfully tested samples showed CNVs. Duplications accounted for 9.5% of the analyzed samples (eight cases), while heterozygous or hemizygous deletions were present in three cases (3.6%). Among all the detected CNVs, only three were certainly pathogenic (3.6%), with two deletions associated with DiGeorge-2 syndrome and Rett syndrome, respectively, and a 2q23.1 microduplication syndrome, all detected in early pregnancy loss samples. For the remaining cases, additional genetic tests (e.g., aCGH/SNP microarray) are required to establish CNV size and gene content and therefore their pathogenicity. Conclusions: MLPA assays seem to have limited value in detecting supplementary chromosomal abnormalities in miscarriages.