Research Projects

VEXAs is a novel hematoinflammatory disorder characterized by somatic mutations in the UBA1 gene of the ubiquitylation pathway. A significant proportion of patients with clinical presentations similar to VEXAs syndrome test negative for the UBA1 mutation, suggesting they might harbor mutations of other genes coding for enzymes of the ubiquitylation pathway other than UBA1. Patients with UBA1 mutation-negative VEXAs syndrome are classified as VEXAs-like syndrome without any known genetic mutations. A prospective study with a comprehensive genomic characterization of patients with UBA1 mutation-negative VEXAs-like syndrome might decode the genetic basis in such patients. The study aims to decipher the molecular genetic basis of UBA1 mutation-negative VEXAs syndrome patients through a targeted next-generation sequencing approach. Around 108 genes of the ubiquitylation pathway will be targeted for the identification of novel pathogenic variants. The clinical, inflammatory, hematological, and genetic profiles of these patients will be studied in detail and compared to the prototype UBA1 mutation-positive VEXAs syndrome patients. This first-of-its-kind prospective study will contribute to the prevalence of VEXAs syndrome/VEXAs-like syndrome from the Indian subcontinent and contribute to world statistics.