All in the Family: Faulty Gene Can Lead to Brain Disease
A gene that helps proteins migrate in and out of the cell's nucleus can mutate and put some families at higher risk for the degenerative brain disease acute necrotizing encephalopathy (ANE).
That is the conclusion of a study led by a researcher from Cincinnati Children’s Hospital Medical Center that was published in the January 9, 2009 issue of American Journal of Human Genetics.
Researchers investigated cases where otherwise healthy children developed ANE soon after contracting common childhood infections like flu. ANE is known for causing neurologic injury; it progresses rapidly with symptoms that include cough, vomiting and diarrhea along with neurologic dysfunction, alteration of consciousness and seizures. ANE is often fatal, or can lead to long-term health problems.
The study showed the children who developed ANE had mutations of the RANBP2 gene, a gene important to cell function. Other members of the children's families also carried the same mutation, said lead investigator Derek Neilson, MD, of the Division of Human Genetics at Cincinnati Children's.
How the mutation leads to ANE in predisposed families and individuals is still unclear, according to the research team, which included investigators from 30 institutions in the US and overseas.
The gene mutation in itself is insufficient to cause full-blown ANE1. Additional genetic and environmental factors – such as the biological route the virus takes and a person's nutritional status – may also be important considerations.
"This study opens new avenues of research, especially our unexpected finding that a missense mutation in part of the nuclear pore predisposes individuals to infection-triggered neurologic disease," said Dr. Neilson. "In order to prevent or lessen the neurological damage caused by ANE, it's important to determine how missense mutations in RANBP2 predispose certain people to the disease."
In a missense gene mutation, the gene's DNA is reconfigured so that certain amino acids are replaced, one for another. This change can remove a protein's function or, theoretically, set off biological chain reactions that lead to disease.
Funding support for the study came from the National Institutes of Health, the Howard Hughes Medical Institute and the Burroughs Welcome Fund.
