TY - JOUR T1 - Pathogenic <em>UBA1</em> variants associated with VEXAS syndrome in Japanese patients with relapsing polychondritis JF - Annals of the Rheumatic Diseases JO - Ann Rheum Dis SP - 1057 LP - 1061 DO - 10.1136/annrheumdis-2021-220089 VL - 80 IS - 8 AU - Naomi Tsuchida AU - Yosuke Kunishita AU - Yuri Uchiyama AU - Yohei Kirino AU - Makiko Enaka AU - Yukie Yamaguchi AU - Masataka Taguri AU - Shoji Yamanaka AU - Kaoru Takase-Minegishi AU - Ryusuke Yoshimi AU - Satoshi Fujii AU - Hideaki Nakajima AU - Naomichi Matsumoto Y1 - 2021/08/01 UR - http://ard.bmj.com/content/80/8/1057.abstract N2 - Objectives To determine clinical and genetic features of individuals with relapsing polychondritis (RP) likely caused by pathogenic somatic variants in ubiquitin-like modifier activating enzyme 1 (UBA1).Methods Fourteen patients with RP who met the Damiani and Levine criteria were recruited (12 men, 2 women; median onset age (IQR) 72.1 years (67.1–78.0)). Sanger sequencing of UBA1 was performed using genomic DNA from peripheral blood leukocytes or bone marrow tissue. Droplet digital PCR (ddPCR) and peptide nucleic acid (PNA)-clamping PCR were used to detect low-prevalence somatic variants. Clinical features of the patients were investigated retrospectively.Results UBA1 was examined in 13 of the 14 patients; 73% (8/11) of the male patients had somatic UBA1 variants (c.121A&gt;C, c.121A&gt;G or c.122T&gt;C resulting in p.Met41Leu, p.Met41Val or p.Met41Thr, respectively). All the variant-positive patients had systemic symptoms, including a significantly high prevalence of skin lesions. ddPCR detected low prevalence (0.14%) of somatic variant (c.121A&gt;C) in one female patient, which was subsequently confirmed by PNA-clamping PCR.Conclusions Genetic screening for pathogenic UBA1 variants should be considered in patients with RP, especially male patients with skin lesions. The somatic variant in UBA1 in the female patient is the first to be reported.Data are available upon reasonable request. The datasets used and analysed during the current study are available from the corresponding author upon reasonable request. ER -