STRs database » HTT locus
Overview of repeats
The normal length of CAG repeats in the HTT gene is below 27 repeats (Testa & Jankovic (2019)) while the low end has been shown to be 9 repeats (Read (1993)). Allele lengths 40 or more repeats causes Huntington’s disease (HD) and is fully penetrant, however, the disease may also occur in individuals with 36-39 repeats in which case they often encounter later age of disease onset and slower progression (Testa & Jankovic (2019)). The number of CAG repeats is negatively correlated with the age of motor onset (Gusella et al. (2014)).
Intermediate alleles in the range of 27-35 have been associated with normal phenotype, but it has been shown that some of the transmission of these alleles were unstable and expanded to the pathogenic range (Semaka et al. (2010)).
In human post-mortem brain tissue, Handsaker et al. (2025) found somatic expansion from inherited alleles of approximately 40-45 CAG repeats to more than 100-500 repeats in striatal projection neurons. Neurons with more than approximately 150 repeats showed loss of neuronal-identity gene expression and activation of senescence or apoptosis-related programmes. These measurements concerned somatically expanded neuronal alleles, rather than inherited repeat-size categories.