Clinical Manifestations of VEXAS Syndrome Across a Broad Spectrum of UBA1 Mutation Burden.

ABSTRACT:

Objective

Vacuoles, E1-ubiquitin-activating enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is a progressive systemic autoinflammatory disorder caused by somatic variants in UBA1 in blood. Previous analyses have shown discordant disease penetrance. In this study, we examine the associations between demographic features and UBA1 variant allele frequency (VAF) with disease manifestations.

Methods

Whole exome sequencing data from 192,584 participants from Geisinger MyCode Community Health Initiative and Mount Sinai BioMe Biobank were analyzed for disease-causing variants in UBA1. Clinical manifestations were analyzed across individuals with the UBA1 variant.

Results

Nine UBA1 variants (VAF range 2.9%-79%) in 23 participants (69.6% men) were identified. Cases

SUBMITTER: Anderson M 

PROVIDER: S-EPMC12906865 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature