Mutant Gene Raises Risk of Parkinson's
Fivefold Higher Parkinson's Risk With Gaucher's Disease Gene
Oct. 21, 2009 -- A clue from a rare disease has led to the discovery of gene
mutations that increase risk of Parkinson's disease fivefold.
People with Gaucher's disease have a defective GBA gene. Doctors studying
the rare, inherited illness noticed that these patients are at increased risk
of the much more common Parkinson's disease.
It's clear that a mutant GBA gene doesn't doom a person to Parkinson's. If
it did, everyone with Gaucher's disease would also have Parkinson's. But could
the gene predispose a person to Parkinson's?
NIH researcher Ellen Sidransky, MD, thought so. So she contacted virtually
every other Gaucher's disease researcher -- 64 of them at 16 centers around the
globe -- to collaborate in a massive study.
"Having mutations in the GBA gene puts you at risk of Parkinson's disease,"
Sidransky tells WebMD. "And five times more Parkinson's patients have this than
An individual's genetic background also plays a role. GBA mutations are
particularly common in Ashkenazi Jews. However, not everyone with a mutant form
of GBA gets Parkinson's.
"I am pretty convinced that not every patient with this mutation will go on
to get Parkinson's disease," Sidransky says. "So there are clearly other
environmental or genetic factors that play into the equation."
What is it about the GBA gene that's linked to Parkinson's? It's known that
the gene encodes an enzyme, glucocerebrosidase or GBA. But what role GBA plays
in Parkinson's disease isn't yet known.
"The ultimate challenge is to establish the mechanism contributing to this
association," Sidransky and colleagues note in their report, which appears in
the Oct. 22 issue of The New England Journal of Medicine.
That search represents an entirely new and promising avenue of research.
"It gives us new theories and ideas that have all kinds of clinical and
therapeutic implications," Sidransky says. "This is a great example of why it
is important to study rare genetic disorders. Because sometimes you end up with
findings that have implications not only for the rare disorder but also for a