Gene linked to rare disease in kids found

New York: In what may help treat a rare but devastating auto-inflammatory condition in children, researchers have identified a gene that may cause the disease named STING-associated vasculopathy with onset in infancy (SAVI).

Auto-inflammatory diseases are a class of conditions in which the immune system, seemingly unprovoked, becomes activated and triggers inflammation.

Normally, the inflammatory response helps quell infections but the prolonged inflammation that occurs in these diseases can damage the body.

DNA comparison of participants revealed a novel mutation in a gene that encodes a protein called STING, a known signalling molecule whose activation leads to production of interferon, a key immune regulator. In excess, however, interferon can trigger inflammation.

"Blood tests on the affected children had shown high levels of interferon-induced proteins, so we were not surprised when the mutated gene turned out to be related to interferon signalling," said Raphaela Goldbach-Mansky from National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) in the US.

When the researchers tested the DNA of patients with similar symptoms, they found mutations in the same gene, confirming STING's role in the disease.

The excessive inflammation observed in patients, along with other evidence of interferon pathway activation, indicated that the mutations in STING boosted the protein's activity.

The researchers found that STING was present in high levels in the cells lining the blood vessels and the lungs, which would likely explain why these tissues are predominantly affected by the disease.

"Not only do these discoveries have profound implications for children with SAVI, but they could have a broader impact by helping us to understand other, more common inflammatory conditions," said NIAMS director Stephen I. Katz.

The study appeared in the New England Journal of Medicine.