Identification of DNA sequence variants in the Vasculo-Behcet disease patient using whole exome sequencing: a pilot...

Vasculo-Behcet disease (VBD) is a complex form of systemic vasculitis with an unclear etiology. It is believed to arise from a combination of immune dysregulation, genetic susceptibility, and epigenetic influences. The disease can be life-threatening due to severe vascular complications such as occlusions, thrombosis, and aneurysm formation. This study aimed to explore the relationship between clinical manifestations and genetic findings in a patient with VBD from Pakistan, where awareness and genetic research on this condition remain limited. Five patients with clinically confirmed VBD were evaluated, and whole exome sequencing (WES) was performed in one patient to investigate potential disease-associated variants. All patients showed evidence of vascular inflammation. Cerebral venous sinus thrombosis (CVST) was observed in three patients, while aneurysm, ST, venous stasis ulcer, and stroke were each identified in two. One patient presented with venous stasis thrombosis together with pulmonary and non-pulmonary arterial thrombosis and macroangiopathic ischemic changes. WES identified nineteen rare nonsynonymous variants (minor allele frequency < 1%) across nineteen genes. Phenotype-based database analysis identified four genes - DPEP1, DNAH5, RHOD, and LRP2 - with reported associations with vascular disorders. Pathway enrichment analysis using ClueGO highlighted seven genes - PAK2, RHOD, MST1, NPHS1, STAR, SLC25A5, and LRP2. Together, these analyses prioritized nine candidate genes with potential relevance to vascular pathology in VBD. Notably, variants in DPEP1 (c.750 C > G, p.Asp250Glu), DNAH5 (c.4807 C > A, p.Pro1603Thr), RHOD (c.244 C > T, p.Arg82Trp), and LRP2 (c.2636G > C, p.Trp879Ser) corresponded to the vascular manifestations observed in our patients, including thrombosis and vessel inflammation. As WES was performed in only one patient, these genetic findings should be considered exploratory. Nevertheless, the results provide preliminary insight into the genetic background of VBD in the Pakistani population and highlight candidate genes that warrant further investigation in larger patient cohorts.