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

Area of Science:

• Genetics
• Molecular Biology
• Clinical Medicine

Background:

• 1p36.33 duplications present variable clinical manifestations based on size.
• This chromosomal region is susceptible to copy number variants (CNVs) linked to diverse phenotypes.
• 1p36 deletions are associated with a known syndrome, but duplications are less characterized.

Purpose of the Study:

• To report a novel 1p36.33p36.32 duplication in a patient.
• To investigate the molecular basis of the observed phenotype using integrative bioinformatic analyses.
• To expand the understanding of the phenotypic spectrum associated with 1p36 duplications.

Main Methods:

• Whole-genome Oligo-array comparative genomic hybridization (CGH) for initial detection.
• Real-time polymerase chain reaction (PCR) for confirmation.
• Integrative bioinformatic analyses including network analysis, phenotype-driven gene prioritization, and dosage sensitivity assessment.

Main Results:

• A 2.3 MB gain in the 1p36.33p36.32 region was identified in a patient presenting with tonic seizures, developmental delay, and facial dysmorphism.
• Bioinformatic analyses highlighted candidate genes such as GABRD, DVL1, and GNB1, known to be involved in neurodevelopmental and congenital disorders.
• Pathway enrichment analysis indicated significant involvement of the '1P36 Copy Number Variation Syndrome' pathway.

Conclusions:

• This case represents a novel 1p36.33p36.32 duplication, expanding the phenotypic spectrum of 1p36 copy number variations.
• The findings underscore the importance of integrating clinical, genomic, and bioinformatic data for precise interpretation of CNVs.
• Further research into 1p36 duplications is warranted to fully elucidate their role in neurodevelopmental disorders.