Rare, severe flu may be explained by gene mutations: study

A previously unknown genetic mutation that disrupts human immune systems can cause rare but potentially life-threatening influenza in some children, a study of a young French girl and her parents said Thursday.

The findings, published in the U.S. journal Science, generally suggested that genetic mutations could be the root cause of some severe forms of influenza in children.

While most people recover from flu after a week, it can be a very severe disease, and even fatal in rare cases, with no reason for doctors to have expected such an outcome.

Researchers at the Laboratory of Human Genetics of Infectious Diseases, a joint French-American international laboratory, proposed a hypothesis that severe influenza in healthy children might be the result of genetic errors.

To test this hypothesis, they sequenced the entire genome of a seven-year-old child, who had contracted a severe form of influenza, requiring her admission to a pediatric intensive care unit in January 2011, at the age of two and a half years.

This analysis, combined with analysis of her parents' genomes, made it possible to show that the little girl had inherited a mutated copy, or allele, of the gene encoding interferon regulatory factor (IRF7) from both of her parents.

That means both copies of her gene that encodes IRF7, a transcription factor known to amplify the production of interferons in response to viral infection in mice and humans, were mutated.

Testing the child's cells in culture, the researchers discovered that many of her skin and immune cells failed to produce type I and III interferons in response to influenza, allowing the virus to replicate more or less unchecked.

Her parents also carried mutations in this gene but at the same time each of them had a normal copy of IRF7, so it's of no consequence.

"In conclusion, we provide proof-of-principle that single-gene inborn errors of immunity can cause severe childhood influenza," the researchers wrote in their paper. "(Interferon)-based, patient- tailored, therapeutic strategies could be helpful in life- threatening influenza of childhood." Endite