A Population-Wide Exploration of the THAP11 CAG Repeat Size and Structure in the 100,000 Genomes Project and UK Biobank

Background: A CAG repeat expansion in THAP11 was recently found to be associated with spinocerebellar ataxia in two Chinese families. Expanded repeats ranged from 45 to 100 units, with CAA sequence interruptions in the 5′ region and an uninterrupted CAG tract in the 3′ tail. Objective: Here, we assess the population distribution of the THAP11 repeat, and its contribution to neurological diseases. Methods: We interrogated data from 54,788 individuals from Genomics England, 10,686 patients from the UCL Queen Square Institute of Neurology in-house database (UCL IoN), and 424,340 individuals from the UK Biobank. Results: We identified expanded repeats in four individuals with learning difficulties without ataxia and in three individuals in UK Biobank, one with hereditary ataxia, one with hereditary neuropathy, and one with neurodegenerative disease. We showed a linear relationship between the number of CAA interruptions and overall repeat length. Conclusions: These results indicate that THAP11 expansions are rare in the British population and that sequence structures predisposed to expansions may be more common in non-British ancestries.