It has long been known that the mutation Huntington’s patients inherit is a longer repeated tract of the nucleotide sequence CAG in their Huntingtin gene.
Healthy people have up to 36 repeats, whereas individuals with 40 or more repeats will go onto develop the disease. However, up until recently it was not known what caused the significant variability in the age at which Huntington’s symptoms first appear or the rate the disease progressed.
Academic research into the underlying mechanisms has converged with human genetic profiling of Huntington’s disease families to throw the spotlight on DNA mismatch repair (MMR) processes. It is not just the length of the CAG repeat mutation that is inherited, but also how prone to further expansion it is that determines the onset and progression of disease.