Mutations Found that Cause Neurologic Disorders

Researchers have identified two mutations in the ATCAY gene, which are apparently responsible for a rare inherited neurologic disorder in humans that is closely mimicked in a mouse model.

Cayman ataxia is a recessive congenital ataxia restricted to one area of Grand Cayman Island that is characterized by poor muscle coordination, some degree of mental retardation, uncontrollable head and eye movements, and difficulty speaking or walking. Exploiting previous findings that Cayman ataxia was due to a recessive mutation in a region of 50-100 genes on chromosome 19, investigators at the University of Michigan Medical School (Ann Arbor, USA) compared this region to a span on mouse chromosome 10 that contains the mutation responsible for an ataxic condition called "jittery.” They reported in the October 2003 issue of Nature Genetics that this approach revealed two mutations in a single gene that they called ATCAY (Ataxia, Cayman type). One mutation substituted an amino acid while the other was a splice mutation expressing a nonfunctional, truncated form of caytaxin, the protein expressed by the gene.

"We do not know what this protein does, but it does not appear to affect the physical development or structure of the brain or nervous system in mice, which appeared completely normal,” explained senior author Dr. Margit Burmeister, associate professor of psychiatry and human genetics in the University of Michigan Medical School. "Unlike other ataxias, there were no neurodegenerative changes. If we can determine caytaxin's function, that will tell us why these people have ataxia, which would be a major step toward finding ways to prevent or treat the disorder.”