Date of Award

5-2024

Document Type

Thesis - Open Access

Degree Name

MS in Human Genetics

First Advisor

Janelle Villiers

Second Advisor

Anna Cantor

Abstract

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is an adult-onset inflammatory condition. Initially thought to only affect males with a specific myeloid-lineage UBA1 somatic mutation, it was hypothesized that females with the same pathogenic mutation might have a milder form of the condition due to its X-linked inheritance. However, recent research has demonstrated that the genotypic and phenotypic profile of VEXAS patients is expanding, with a recent subset of female patients being identified. This literature review investigates the clinical features and UBA1 somatic mutations in females with VEXAS, aiming to understand how the condition presents in females compared to males. Notably, this review identified that although VEXAS syndrome presents at a lower frequency in females, the clinical features are similar. The most frequent symptoms among our literature-based cohort in both sexes were rheumatological symptoms. Gastrointestinal involvement and fatigue was exclusively reported in male patients with VEXAS, and the c.122T>C, p.Met41Thr somatic mutation was the most common mutation identified in both sexes. Overall, the findings of this review indicate that female patients who meet the criteria for relapsing polychondritis and/or myelodysplastic syndrome, and have any of the following symptoms: macrocytic anemia, thrombocytopenia, arthritis, fever, chondritis, should undergo somatic UBA1 genetic testing. Further research with female patients is needed to expand the clinical picture of this disease, and to understand how VEXAS syndrome manifests in this population.

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