Leuven researchers describe in which a genetic mutation causes the increase of another mutation. The article was recently published in the New England Journal of Medicine.
Auto-inflammatory disorders are complex disorders that cause inflammatory reactions and fever as a result of excess activitiy of our immune system. The inflammation can occur spontaneously without an inciting factor, hence the name auto-inflammation. Sometimes the inflammation is due to underlying genetic abnormalities that already result in symptoms from childhood onwards. Very little is known about auto-inflammation in adulthood.
Leuven doctors and researchers have now described a new mechanism to explain the phenomenon. Extensive genetic and immunological research in a patient with an unexplained clinical picture shows that the patient is carrier of a mutation in a gene that can cause auto-inflammation (NLRC4). Surpisingly, this mutation could only be found in a fraction of the cells and occurs in adulthood. Further research showed that the mutant cells continued to increase over the years as a result of a second mutation in TET2. That second mutation proved to be the cause of the increase in mutant cells.