Exploratory whole-exome sequencing identifies candidate DNA variants in Ocular Behcet disease: a pilot study from a...

Ocular Behcet disease (OBD) is a severe sight-threatening complication of Behcet disease (BD) with a poorly understood etiology, particularly in underrepresented populations such as Pakistan. It often arises from a combination of genetic predisposition, environmental triggers, and immune dysregulation. To address this gap, we explored genetic variants contributing to ocular involvement using whole-exome sequencing (WES).

Eleven clinically diagnosed BD patients were recruited, including ten with ocular symptoms such as uveitis, diplopia, and optic nerve involvement. WES was performed on five individuals, and rare, potentially damaging nonsynonymous variants were prioritized using in silico tools and annotated through ClinVar, MalaCards, GeneCards, and HGMD.

Seventeen genes were found associated with ocular manifestations. Pathway enrichment (ClueGO) and regulatory variant analysis (RegulomeDB, score <3) were applied to identify pathways in OBD. Five genes, LRP2, NPHS1, DSCAM, MST1 and PAK2 were prioritized for their roles in immune regulation and maintaining ocular and neurovascular homeostasis. These genes carried variants with potential impact, while RegulomeDB highlighted two regulatory variants in LRP2.

This study provides the first genetic profile of OBD in Pakistani patients, identifies rare candidate genes of relevance, and establishes a foundation for larger confirmatory studies with implications for genetic screening.