MADISON - Scientists have pinpointed the gene responsible for a rare and devastating childhood brain disorder called Alexander disease, solving a 50-year-old mystery regarding its cause.
Reporting in the January 3 issue of the journal Nature Genetics, a team led by University of Wisconsin-Madison researcher Albee Messing made the discovery after a genetic analysis of 13 cases of the disease. Because of the rarity of the disease, it took nearly two years to assemble enough cases from international sources to complete the study.
Alexander disease is in a family of disorders called leukodystrophies in which abnormalities arise in the myelin sheath, a protective insulation that covers nerves. It often strikes infants before their first year of age and causes catastrophic damage throughout the nervous system. Most children do not survive past age 6.
While genetics were always presumed to be the cause, confirming the hunch would have been impossible without an unexpected break several years ago in Messing's lab. Messing and collaborator Michael Brenner of the University of Alabama-Birmingham developed a transgenic mouse that coincidentally exhibited the hallmark traits of Alexander disease, which narrowed the field for finding the responsible gene.
The Nature Genetics paper confirmed that mutations in a gene called GFAP - or glial fibrillary acidic protein - are associated with nearly all cases of Alexander disease. Messing said the mutation triggers production of an abnormal protein, which causes a buildup of fibers that damage the nervous system.
"Finding this gene would have been a shot in the dark without that initial discovery," said Messing. "GFAP is a very well-known and widely studied protein among neuroscientists, because it's the identifying feature of astrocytes."
Astrocytes are one of the major cell types in all vertebrate nervous systems that maintain the function of neurons and their myelin sheaths. Scientists already know that GF
Contact: Albee Messing
University of Wisconsin-Madison