Summary

VEXAS syndrome is an adult-onset inflammatory condition primarily affecting males. Clinical suspicion of VEXAS is molecularly confirmed when a disease-associated somatic variant, in the UBA1 gene, often at the Met41 residue, is identified in a DNA specimen containing myeloid tissue. We present a case series of 17 patients where clinical genetic testing at Blueprint Genetics identified variants affecting the UBA1 Met41 residue, and the next-generation sequencing (NGS) assay validation showed that mosaic variants with an allelic ratio of as low as 14.6% can be detected with greater than 90% probability. The median allelic ratio of variants detected in DNA extracted from blood and bone marrow (62%) in the studied cases is consistent with the medical literature to date, while lower allelic ratios were seen in analysis of DNA from the 2 saliva specimens studied. 

These data show that a validated NGS assay can identify UBA1 p.Met41 somatic variants associated with VEXAS syndrome.  

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Authors:

Alicia Scocchia, Allison Sluyters, Margarita Andreevskaya, Kirsi Alakurtti, Päivi Kokkonen, Kimberly Gall, Julie Hathaway, Victoria Howell, Lotta Koskinen, Janica Djupsjöbacka, Massimiliano Gentile, Pertteli Salmenperä, Jussi Paananen, Samuel Myllykangas, Juha Koskenvuo