Researchers at Johns Hopkins have discovered a gene mutation that causes a condition apparently identical to Huntington's Disease, helping to explain why some people with the disorder do not have the mutation found in most cases. The finding may help reveal why some diseases, like Huntington's, Alzheimer's and Parkinson's, destroy some brain cells while sparing others.

"For all practical purposes this is Huntington's Disease, yet it's caused by a different mutation on a completely different chromosome," said Russell L. Margolis, M.D., associate professor of Psychiatry at Hopkins and director of the Laboratory of Genetic Neurobiology.

The new mutation is in a gene called junctophilin-3 on chromosome 16, and the disorder it causes is called Huntington's Disease-like 2 (HDL2). The mutation that causes most Huntington's Disease cases is called huntingtin, and is found on chromosome 4, according to Margolis.

The scientists don't know how the new mutation affects the gene's function, but they do know that it leads to a pattern of brain cell death identical to Huntington's Disease: the same types of nerve cells are destroyed, the same regions of the brain, called the basal ganglia and the caudate nucleus, are targeted, and one side of the brain is affected more than the other. People with HDL2 also have the same types of changes in emotions, thinking, and decline in motor skills as those with Huntington's Disease. Like Huntington's, HDL2 occurs in mid-adult life and leads to death in about 10 to 20 years.

The type of mutation in the two genes is also similar. Both are repeat expansions, where a small segment of DNA, in this case three consecutive base-pairs, is repeated
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Contact: Trent Stockton
tstockt1@jhmi.edu
410-955-8665
Johns Hopkins Medical Institutions
18-Oct-2002