Here’s how it works. The disease is passed from parent to child through a genetic mutation. The
mutation is a long sequence of repeated CAG nucleotides in the huntingtin gene. The number of
these repeats determines whether or not someone will develop the disease.
Everyone has two copies of the huntingtin gene-one from each parent. People who have 26 or fewer
repeats on both copies of the gene will not develop the disease, nor will any of their children. People
who have one copy of the gene with 40 or more repeats will develop the disease and their children
will have a 50/50 chance of inheriting the gene mutation. Having between 27 and 39 repeats is
known as a “gray area.” People with 36 to 39 repeats have what scientists call a “reduced
penetrance” of the gene. They may or may not develop symptoms of the disease.
Up until now, researchers have studied how common this reduced penetrance is mainly in people
who already have symptoms of the disease and their family members. In this study, researchers use
new genetic testing methods to check for the gene in the general population.
They studied the genes of 7,315 people from Canada, the United States and Scotland. Of those, 18
people had 36 or more repeats, which extrapolates to about 1 in 400 people in the general
population, which is up to 10 times higher than previous estimates. Three of those people had 40 or
more repeats of the gene, which is considered full penetrance. That number was consistent with
The study also suggests that the penetrance of the disease among people with 36 to 38 repeats is
lower than previously thought, meaning that fewer people in this group would develop symptoms of
the disease. For people over the age of 65, the researchers estimate that 0.2 percent of those with 37
repeats would have symptoms of the disease, compared to the 10 percent that was previously
estimated. For those with 38 repeats, an estimated 2.0 percent of those over 65 would have
symptoms, compared to the 19 percent previously estimated.
Study author Michael R. Hayden, MB ChB, PhD, who is a professor at the University of British
Columbia in Vancouver, Canada, and also president of global research and development and chief
scientific officer at Teva Pharmaceuticals, said, “It’s unclear why some people with reduced
penetrance genes develop the symptoms of Huntington’s as early as midlife, while others reach old
age with no symptoms. Additional genetic and environmental factors may modify the likelihood that
a person develops the disease.”
Hayden noted that while people with reduced penetrance may be at relatively low risk of developing
the disease themselves, they may play a larger role in transmitting the full penetrance gene to the
next generation than was previously understood.
The study was supported by the Canadian Institutes of Health Research.
To learn more about Huntington’s disease, please visit http://www.aan.com/patients.
The American Academy of Neurology, an association of 30,000 neurologists and neuroscience
professionals, is dedicated to promoting the highest quality patient-centered neurologic care. A
neurologist is a doctor with specialized training in diagnosing, treating and managing disorders of
the brain and nervous system such as Alzheimer’s disease, stroke, migraine, multiple sclerosis,
concussion, Parkinson’s disease and epilepsy.
For more information about the American Academy of Neurology, visit http://www.aan.com or find
us on Facebook, Twitter, Google+ and YouTube.