The VEXAS syndrome from rheumatology perspective: genomic DNA sequencing as available blueprint for diagnosing rheumatic diseases with overlapping haematological or dermatological findings

Excerpt

The discovery of the VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome in 2020 using a genotype-driven approach to identify an adult inflammatory syndrome may have useful diagnostic and clinical implications for the rheumatology patients. Beck et al. reported that this adult inflammatory syndrome was associated with the presence of an X-linked ubiquitin-activating enzyme 1 (UBA1) genetic somatic mutation in 25 adult patients identified by the genetic DNA sequencing technique [1]. The condition was uncovered following a review of genomes of 1083 patients with unexplained clinical features of either an inflammatory syndrome (chondritis, alveolitis or skin rash) or a hematologic condition (myelodysplastic syndromes) or both as part of the undiagnosed disease programme [2, 3]. Characteristically, VEXAS syndrome was revealed only in men who have one copy of the X-chromosome. Heterozygous variants of the X-linked gene UBA1 revealed in three men raised the suspicion of mutation. Consequently, the researchers continued their examination of the remaining patients with suspected VEXAS syndrome—utilising a genomic DNA sequencing approach to highlight the features and insight of the condition [1]. …