VEXAS without vacuoles: Linking genotype to phenotype

Area of Science:

• Hematology
• Genetics
• Pathology

Background:

• VEXAS syndrome is a rare autoinflammatory disorder caused by somatic mutations in the UBA1 gene.
• A key diagnostic feature is cytoplasmic vacuolization in bone marrow hematopoietic cells.

Purpose of the Study:

• To report a case of VEXAS-associated myelodysplastic syndrome with a non-canonical UBA1 mutation.
• To investigate the significance of cytoplasmic vacuolization in VEXAS syndrome.

Main Methods:

• Case report of a male patient diagnosed with VEXAS-associated myelodysplastic syndrome.
• Genetic analysis revealing a non-canonical UBA1 p.Gly477Ala variant.
• Bone marrow biopsy examination.

Main Results:

• The patient's bone marrow biopsy showed a lack of cytoplasmic vacuolization in hematopoietic cells.
• Confirmed VEXAS-associated myelodysplastic syndrome despite absent vacuolization.

Conclusions:

• Cytoplasmic vacuolization may not be a mandatory feature for VEXAS syndrome diagnosis.
• This case expands the understanding of UBA1 mutations and VEXAS pathobiology.