Atypical splice-site mutations causing VEXAS syndrome
Marie Templé, Eugénie Duroyon, Carolyne Croizier, Julien Rossignol, Thomas Huet, Chloé Friedrich, Loria Zalmaï, P. Priollet, Gilles Hayem, Olivier Tournillhac, G. Le Guenno, Olivier Hermine, Benjamin Terrier, Olivier Kosmider
Abstract
Dear Editor, Recently described in male patients [1], somatic UBA1 (Ubiquitin Like Modifier Activating Enzyme 1) mutations affecting methionine 41 (M41) are now considered as key features of a new autoinflammatory disorder called VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic). Other UBA1 point mutations have recently been described, affecting the mainly splice acceptor site of exon 3 leading to a truncated form of UBA1 [2, 3] and in only one case a mutation of serine 56, leading to a slightly different form of VEXAS syndrome [3]. Discovery of UBA1 mutations provided new insights into the pathogenesis of inflammatory disorders like relapsing polychondritis [4, 5] or severe joint involvment [6]. Moreover, rare cases have also been very recently reported in female patients [5], with an association to acquired X monosomy [7, 8]. We present here two male patients (unique patient numbers UPN1 and UPN2) who present atypical splice-site mutations of UBA1 in a context of VEXAS syndrome.