"VEXAS syndrome is caused by somatic (acquired) mutations, typically missense mutations, to the UBA1 gene in haematopoietic progenitor cells of the erythroid and myeloid lineages 1-3. The UBA1 gene is encoded on the X chromosome and escapes X inactivation in females, which is why it is almost exclusively seen in males 1-3, and only seen in females in the context of monosomy X 5. UBA1 encodes for the E1 enzyme, a ubiquitin activating enzyme, which when defective in haematopoietic progenitor cells leads to activation of the innate immune system, and thus, autoinflammatory clinical manifestations 1-3. Certain UBA1 mutations may be associated with specific phenotypes, for example, p.Met41Leu variants are associated with Sweet syndrome, and p.Met41Val variants are associated with vasculitic dermatological lesions and less associated with chondritis 9."
"VEXAS syndrome is caused by somatic (acquired) mutations, typically missense mutations, to the UBA1 gene in haematopoietic progenitor cells of the erythroid and myeloid lineages 1-3. The UBA1 gene is encoded on the X chromosome and escapes X inactivation in females, which is why it is almost exclusively seen in males 1-3, and only seen in females in the context of monosomy X 5. UBA1 encodes for the E1 enzyme, a ubiquitin activating enzyme, which when defective in haematopoietic progenitor cells leads to activation of the innate immune system, and thus, autoinflammatory clinical manifestations 1-3. Certain UBA1 mutations may be associated with specific phenotypes, for example, p.Met41Leu variants are associated with Sweet syndrome, and p.Met41Val variants are associated with vasculitic dermatological lesions and less associated with chondritis 9."
"VEXAS syndrome is caused by somatic (acquired) mutations, typically missense mutations, to the UBA1 gene in haematopoietic progenitor cells of the erythroid and myeloid lineages 1-3. The UBA1 gene is encoded on the X chromosome and escapes X inactivation in females, which is why it is almost exclusively seen in males 1-3, and only seen in females in the context of monosomy X 5. UBA1 encodes for the E1 enzyme, a ubiquitin activating enzyme, which when defective in haematopoietic progenitor cells leads to activation of the innate immune system, and thus, autoinflammatory clinical manifestations 1-3. Certain UBA1 mutations may be associated with specific phenotypes, for example, p.Met41Leu variants are associated with Sweet syndrome, and p.Met41Val variants are associated with vasculitic dermatological lesions and less associated with chondritis 9."
"ANCA-associated vasculitis (rare)"
"VEXAS syndrome is caused by somatic (acquired) mutations, typically missense mutations, to the UBA1 gene in haematopoietic progenitor cells of the erythroid and myeloid lineages 1-3. The UBA1 gene is encoded on the X chromosome and escapes X inactivation in females, which is why it is almost exclusively seen in males 1-3, and only seen in females in the context of monosomy X 5. UBA1 encodes for the E1 enzyme, a ubiquitin activating enzyme, which when defective in haematopoietic progenitor cells leads to activation of the innate immune system, and thus, autoinflammatory clinical manifestations 1-3. Certain UBA1 mutations may be associated with specific phenotypes, for example, p.Met41Leu variants are associated with Sweet syndrome, and p.Met41Val variants are associated with vasculitic dermatological lesions and less associated with chondritis 9."
"VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a severe, treatment-refractory, monogenic, multiorgan, autoinflammatory condition with vasculitic and haematological complications."
"VEXAS syndrome has an incredibly varied clinical presentation 9. Overall, the most common symptoms are dermatological (~80%), constitutional (~70%), respiratory (~60%), musculoskeletal (~50%), ocular (~40%), chondritis (~40%), and haematological (~40%) 9. Broadly, these clinical manifestations may be broadly divided into inflammatory and haematological:"
"skin inflammation (e.g. panniculitis)"
"dyspnoea (e.g. due to alveolitis, organising pneumonia)"
"ocular inflammation (e.g. orbital inflammation, episcleritis, scleritis, uveitis, optic perineuritis)"