Somatic Mutations in Rheumatology: The Paradigm of Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic (VEXAS) Syndrome
Year: 2025
Type: article
Abstract: Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic syndrome is a recently recognized adult-onset autoinflammatory disease caused by somatic mutations in the ubiquitin-like modifier-activating enzyme 1 ( UBA1) gene on the X chromosome, primarily affecting older males. It presents with systemic inflammation, relapsing polychondritis, vasculitis, neutrophilic dermatoses, macrocytic anemia, and characteristic bone marrow vacuoles. The disorder is often resistant to standard immunosuppression and may co-occur with clonal hematopoiesis mutations like TET2 and DNMT3A . Management includes glucocorticoids, JAK inhibitors, interleukin-6 blockers, and hypomethylating agents, while hematopoietic stem cell transplantation is being explored as a potential cure. VEXAS underscores the significance of somatic mutations in adult inflammatory syndromes.
Source: Genetic Clinics
Authors: Suranjana Banik, Sumita Danda
Institution: Christian Medical College, Vellore
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
OpenAlex ID: W4411420855