Dear Editor, The VEXAS syndrome (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) is a recently described autoinflammatory disease characterized by mutations in the E1 ubiquitin-activating ...enzyme encoded by the UBA1 gene 1. Clinico-biological findings include haematological abnormalities, treatment-refractory inflammatory syndrome, skin lesions, thromboembolic events, pulmonary infiltrate and chondritis 1–3. To date, hundreds of patients have been described in the literature, with most subjects harbouring a single mutation in UBA1 4–6. In their first cohort, Beck et al. identified recurrent UBA1 mutations all affecting methionine 41 of exon 3 of UBA1: p. M41T (c.122T>C), p. M41V (c.121A>G) and p. M41L (c.121A>C) 1. Since this initial description, other mutations have been reported, such as splice region mutations at exon 3 (c.118-2A>C, c.118-1G>C and C.118-9_118-2del) as well as a mutation affecting serine 56 in exon 3 (c.167C>T) 7. The mutation of the UBA1 gene is considered to be the initiating event of VEXAS syndrome. However, the mechanisms leading to its emergence are unknown and are therefore, by default, mainly considered as a Darwinian process with random occurrence and clonal expansion in haematopoietic cells as a product of natural selection.
