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National Institutes of Health (NIH) researchers reported a newly discovered deadly inflammatory disorder last week.
“We had many patients with undiagnosed inflammatory conditions who were coming to the NIH Clinical Center, and we were just unable to diagnose them,” Dr. David Beck, a clinical fellow at NHGRI and lead author of the paper, said in a news release. “That’s when we had the idea of doing it the opposite way. Instead of starting with symptoms, start with a list of genes. Then, study the genomes of undiagnosed individuals and see where it takes us.”
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The team examined over 2,500 people with undiagnosed inflammatory diseases and assessed over 800 genes involved in cells’ regulatory processes, per the release.
In doing this, they found one mutated gene, UBA1, causing the syndrome dubbed VEXAS for “vacuoles, E1 enzyme, X-linked, autoinflammatory and somatic syndrome.”
Nearly half the patients under study died from the serious condition, researchers said. (iStock)
“So far, 40% of VEXAS patients who the team studied have died, revealing the devastating consequences of the severe condition,” per the release. The disease involves blood clotting, repeated fevers, heart issues and problems with blood cells, called myeloid cells.
Findings were published in the New England Journal of Medicine.
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“Our objective was to see if any of the 2,560 patients shared variations in the same gene,” Dr. Daniel Kastner, scientific director of the Intramural Research Program at NHGRI and a senior author of the paper, said in a news release. “Instead of looking at clinical similarities, we were instead taking advantage of shared genomic similarities that could help us discover a completely new disease.”
Of the 2,560 patients, researchers said 1,000 had repeated fevers and widespread inflammation. Three men had the mutated gene in the X chromosome; men have one X chromosome and one Y chromosome, while women have two X chromosomes.
Researchers found “mosaicism” among the affected patients, which happens when some cells carry the gene in its mutated form, and other cells carry the gene in its normal form, per the release. Ultimately, 25 total men across other NIH databases showed to have the mutated gene with similar symptoms: blood clotting, repeated fevers and heart issues, among others.
“By using this genome-first approach, we have managed to find a thread that ties together patients carrying all of these seemingly unrelated, disparate diagnoses,” Kastner concluded.
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