Researchers find there are more people with at least 36 repeats of the huntingtin gene than past estimates suggest.
Researchers identified a greater occurrence of “reduced penetrance” – defined as 36-39 repeats of a gene mutation known to cause Huntington’s disease (HD) – among the general population than previously reported.
This means that the number of people who are at low risk of developing HD may be much higher than the current estimate indicates.
However, the study also presents some positive news; older adults with reduced penetrance may be at lower risk of developing symptoms of HD than previously thought.
Study co-author Michael R. Hayden, of the University of British Columbia in Vancouver, Canada, and colleagues recently published their findings in the journal Neurology.
How gene mutation repeats affect HD risk
HD is caused by mutation in the huntingtin gene, characterized by excessive repeats of the building blocks of DNA known as cytosine, adenine, and guanine (CAG).
Fast facts about Huntington’s disease
- HD symptoms most commonly arise between the ages of 30-50
- Symptoms include uncontrolled movements, changes in behavior and cognition, slurred speech, and difficulty swallowing
- There are currently no treatments that can stop or reverse HD.
Each person has two copies of the huntingtin gene – one inherited from each parent.
If an individual has up to 26 CAG repeats in both copies of the gene, they will not develop HD, nor will their offspring.
A person who has one copy of the huntingtin gene with at least 40 repeats – known as “full penetrance” – will develop HD, and there is a 50 percent chance that their offspring will inherit the mutation.
A person with 27-39 repeats in a copy of the huntingtin gene falls into what researchers call a “gray area,” while 36-39 repeats is deemed “reduced penetrance.” This means it is unclear whether these individuals will develop HD or not.
According to Hayden and colleagues, previous studies have mainly investigated how common reduced penetrance is among people who have already developed symptoms of HD, which may not give a true picture of HD risk among the general population.
Older adults with gene repeats may be at lower risk of HD symptoms
For their study, the researchers set out to get a more accurate estimate of HD risk by using a novel genetic testing technique to assess the genes of 7,317 individuals from Canada, the U.S., and Scotland.
The team found that 18 of the study participants possessed at least 36 repeats of the huntingtin gene, which the researchers estimate is the equivalent to around 1 in 400 people in the general population. This is 10 times higher than previous estimates.
But it’s not all bad news; the researchers also found that individuals with 36-38 repeats of the huntingtin gene have a lower risk of developing symptoms of HD than previously estimated.
Additionally, the team found that among people aged 65 and older who had 37 repeats, around 0.2 percent would develop symptoms of HD – significantly lower than the 10 percent previously estimated.
Around 2 percent of adults aged 65 and older who had 38 repeats were likely to develop symptoms of HD. Previous estimates suggested 19 percent of these individuals would develop symptoms.
“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.”
Michael R. Hayden
For people with 40 or more repeats, the team’s estimates matched previous ones.
Hayden notes that while people with reduced penetrance have a low risk of developing HD, they can still pass the gene mutation representing full penetrance onto offspring. This means that future generations might be at greater risk of HD than we thought.