Rapid Screening and Monitoring of UBA1 Mutations in VEXAS Syndrome

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is a severe adult-onset autoinflammatory disease associated with hematologic conditions, such as myelodysplastic syndrome. VEXAS is mostly due to an acquired mutation affecting methionine 41 (p.M41) of the UBA1 gene, which is present in >90% of patients and usually at a high burden. Treatment strategies are diverse, but many aim to suppress the UBA1 mutant clone with hypomethylating agents or by allogeneic hematopoietic cell transplantation. In the present study, we have developed a high-resolution melting tool for rapid detection of UBA1 p.M41 mutations, useful in diagnostic discrimination, and three sensitive real-time allele-specific oligonucleotide PCRs to determine the variant allele frequency of p.M41T/V/L mutations, applicable in the molecular monitoring of the disease.