Investigation of the Influence of TBP CAG/CAA Repeats in Conjunction with HTT CAG Repeats on Huntington's Disease Age at Onset in a Brazilian Sample.

Huntington's disease (HD) is a genetic neurodegenerative progressive and fatal disease characterized by motor disorder, cognitive impairment, and behavioral problems, caused by expanded repeats of CAG trinucleotides in the HTT gene. The aim of this study was to investigate the influence of TBP gene CAG/CAA repeats in conjunction with HTT gene CAG repeats, on the age at HD onset in Brazilian individuals. Individuals diagnosed as molecularly negative for HD presented 29-39 TBP CAG/CAA. Their most frequent allele had 36 repeats. In individuals diagnosed as molecularly positive for HD, a range of 25-40 TBP CAG/ CAA was found. The most frequent TBP allele had 38 repeats. We also conducted TBP direct Sanger sequencing of some samples which demonstrated other four TBP structures different from the basic TBP structure and others reported in the literature. The HTT expanded CAG and TBP CAG/CAA repeat sizes jointly explained 66% of the age at onset (AO) in our HD patients. The strongest variable in the model associated with AO was the number of expanded HTT CAG repeats. The difference between the association of HD AO with HTT expanded CAG together with TBP CAG/CAA and the association of HD AO with HTT expanded CAG was 0.001 (∆R2). Therefore, we found a weak association (0.1%) of TBP CAG/CAA repeats on HD AO, if any. © 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Citation

Iane Dos Santos da Silva, Thays Andrade Apolinário, Luciana de Andrade Agostinho, Carmen Lucia Antão Paiva. Investigation of the Influence of TBP CAG/CAA Repeats in Conjunction with HTT CAG Repeats on Huntington's Disease Age at Onset in a Brazilian Sample. Journal of molecular neuroscience : MN. 2022 May;72(5):1116-1124

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PMID: 35275350

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