Autoinflammatory & rare systemic diseases
Estimated Prevalence and Clinical Manifestations of UBA1 Variants Associated With VEXAS Syndrome in a Clinical Population
Authors' conclusion
This study provides an estimate of the prevalence and a description of the clinical manifestations of UBA1 variants associated with VEXAS syndrome within a single regional health system in the US.
Study context
- Population
- Unselected participants of the Geisinger MyCode Community Health Initiative with exome data; EHR data 1996–2022 (mean age 52.8 years; 94% White; 61% women)exome data
- Participants
- 163,096 participants
- Outcome
- Prevalence of somatic UBA1 variation and associated clinical manifestations
Methodological detailsobservational, genomic ascertainment, exome sequencing, single regional health system
- Observational
- Genomic ascertainment
- Exome sequencing
- Single regional health system
Main finding
As reported in the abstract
Prevalence of disease-causing UBA1 variants
Likely somatic variants at known pathogenic UBA1 positions (individuals)
11
Unrelated individuals
1 in 13 591
95% CI 1:7775–1:23 758
Men older than 50 years
1 in 4269
95% CI 1:2319–1:7859
Women older than 50 years
1 in 26 238
95% CI 1:7196–1:147 669
Observational data: associations, not effects.
Further findings
Clinical manifestations in the 11 variant carriers
- Clinical manifestations consistent with VEXAS syndrome
- 11 of 11 (100%)
- Sex: male / female
- 9 / 2
- Not meeting criteria for rheumatologic and/or hematologic diagnoses previously associated with VEXAS
- 5 of 11 (45%)
- Anemia in all; hemoglobin mean / median
- 7.8 g/dL / 7.5 g/dL
- Macrocytic anemia
- 10/11 [91%]
- Concomitant thrombocytopenia
- 10/11 [91%]
- Pathogenic variant before onset of VEXAS-related signs or symptoms (male)
- 1
- Female participants with disease and heterozygous variants
- 2
- Previously unreported UBA1 variant (c.1861A>T; p.Ser621Cys) in a symptomatic patient, in vitro data supporting catalytic defect and pathogenicity
Original publication
Estimated Prevalence and Clinical Manifestations of UBA1 Variants Associated With VEXAS Syndrome in a Clinical Population. JAMA. Published 24 January 2023. doi:10.
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