Atypical splice-site mutations causing VEXAS syndrome

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.