Age of onset in Huntington's disease is influenced by CAG repeat variations in other polyglutamine disease-associated genes

We read with great interest the recent article by Tezenas du Montcel et al. (2014), who showed that the age of onset in several spinocerebellar ataxias (SCAs) is modulated by CAG repeat sizes in the normal range in other polyglutamine disease-associated genes. Interestingly, the age of onset in patients with SCA3 was also influenced by the CAG repeat size in the HTT gene: long normal HTT CAG repeat size was associated with a delayed age of onset in SCA3 patients (Tezenas du Montcel et al., 2014). Similarly, in a subsequent study in patients with SCA3 from mainland China, it was shown that the difference in CAG repeat size between the two HTT alleles interacted with the ATXN3 expansion and affected age of onset in these patients (Chen et al., 2016).