The average age of onset is 40 years with death occuring about 10-15 years later. The expanded CAG repeat is translated into a polyglutamine tract in the huntingtin protein which is believed to cause a dominant gain of function. But in HD which only develops at an elderly age other factors are involved in determining the age of onset. Instability depends on the length of the CAG repeat in both male and female transmissions.
Instability occurs during gametogenesis, showing a greater instability in male transmissions.
This could be influenced by the continual mitotic divisions during spermatogenesis. The larger the somatic allele, the greater the average allele length of the mutant sperm. However transmission from a HD father can on occasion produce large expansions that cause the juvenile onset form of the disease. These two situations reflect the mosaicism in CAG repeat length in sperm from HD males. A model to explain the instability of the repeat in HD predicts that CAG repeats form stable hairpin structures.