A hitch in the stitch reveals why DNA sequence patterns matter in Huntington’s disease

Publication date: Feb 10, 2026

A new study sheds light on different sequence patterns present that may help explain why some individuals with the same CAG repeat size have such vastly different disease trajectories. If sequence patterns affect both onset and progression, then grouping participants by repeat count alone may unintentionally mix people with very different disease trajectories. Two individuals with the same CAG number may face very different risks depending on their underlying sequence pattern. For individuals in the HD grey zone between 36-39 repeats, an understanding of when symptoms may arise and what kind of symptoms is critical. When compared with common prediction models based on repeat length alone, symptom onset in these individuals occurred nearly 13 years earlier than expected. The biology of the HTT gene, its sequence pattern and how to predict when someone will start symptoms are all extremely complex factors that are under investigation. 5 individuals had an interruption in the C-C-G repeat stretch but not in the CAG stretch meaning the CAG repeat portion doesnt have hitches.