Comprehensive Clinical, Diagnostic, and In Silico Assessment of a Novel 1p36.33p36.32 Copy Number Variant

Clinical manifestations of 1p36.33 duplications vary depending on duplication size. This region is prone to copy number variants associated with diverse phenotypes. We report a novel 1p36.33p36.32 duplication in a patient with developmental delay and facial dysmorphism. The causative duplication was detected by whole-genome Oligo-array CGH and confirmed by real-time PCR. Integrative bioinformatic analyses-including network analysis, phenotype-driven gene prioritisation, and dosage sensitivity assessment-were performed to explore the molecular basis of the phenotype; we used integrative bioinformatic analyses, including network analysis, phenotype-driven gene prioritisation, and dosage sensitivity assessment. Assessment of a child with tonic seizures, developmental delay, and dysmorphic facial traits revealed a 2.3 MB gain in the 1p36.33p36.32 region (nucleotide 898,721 to 3,153,945) through array CGH. Bioinformatic analyses identified several candidate genes, including GABRD, DVL1, and GNB1, which are implicated in neurodevelopmental and congenital disorders. Pathway enrichment analysis revealed significant involvement of the '1P36 Copy Number Variation Syndrome' pathway. This case expands the phenotypic spectrum of 1p36 duplications and highlights the importance of integrating clinical, genomic, and bioinformatic data for accurate interpretation.