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PubMed · 42107927

Assessing the Frequency of VEXAS-Related Canonical UBA1 Mutations in Myelodysplastic Syndrome Patients.

Hadis Soleimanzadeh·Mohammadjafar Sharifi·Mansoureh Shokripour·Jamileh Saberzadeh·Mani Ramzi·Pardis Nematollahi·Nahid Nasiri
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Abstract

OBJECTIVES: Somatic mutations in the UBA1 gene cause VEXAS syndrome, which presents with inflammatory and hematological symptoms. Case studies show a strong overlap between VEXAS and myelodysplastic syndrome (MDS). Recognizing VEXAS is important for differential diagnosis in patients with both inflammation and MDS, as accurate identification guides treatment. The study focuses on determining how often canonical UBA1 mutations linked to VEXAS occur in MDS patients. METHODS: Patients diagnosed with MDS were enrolled in the study, and genomic DNA was isolated from bone marrow FFPE samples. Molecular analysis was performed using a specifically designed ARMS-PCR approach. Additionally, protein-protein interaction (PPI) studies combined with bioinformatic analyses were carried out to explore potential links between UBA1 and pyroptosis. RESULTS: Among the 149 MDS patients analyzed, none exhibited high-Variant Allele Frequency (VAF) the canonical UBA1 point mutations linked to VEXAS syndrome. PPI analysis revealed a possible association between UBA1 and the NLRP3 inflammasome component. CONCLUSIONS: Expanding the sample size and using targeted NGS or ddPCR would improve mutation detection sensitivity and could reveal UBA1 canonical and non-canonical variants and more accurately estimate the frequency of VEXAS-related mutations in the MDS population.

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HumansMyelodysplastic SyndromesUbiquitin-Activating EnzymesMutationGene FrequencyFemaleMaleGenetic Predisposition to DiseaseAgedMiddle AgedAged, 80 and overAdultAllelesDNA Mutational AnalysisGenetic Association StudiesSkin Diseases, GeneticUBA1ARMS‐PCRVEXAS syndromemyelodysplastic syndromeubiquitinationJournal Article

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Hadis Soleimanzadeh, Mohammadjafar Sharifi, Mansoureh Shokripour, Jamileh Saberzadeh, Mani Ramzi, Pardis Nematollahi, Nahid Nasiri. 2026-05-10. Assessing the Frequency of VEXAS-Related Canonical UBA1 Mutations in Myelodysplastic Syndrome Patients.. https://doi.org/10.1111/ejh.70210

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Journal Article resourceAdult subjectAged subjectAged, 80 and over subjectAlleles subjectFemale subjectGene Frequency subjectGenetic Predisposition to Disease subjectHumans subjectJournal Article subjectMale subjectMiddle Aged subjectMutation subject

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