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Investigating TBP CAG/CAA trinucleotide repeat expansions in a Taiwanese cohort with ALS

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posted on 2020-12-30, 12:10 authored by Kang-Yang Jih, Kon-Ping Lin, Pei-Chien Tsai, Bing-Wen Soong, Yi-Chu Liao, Yi-Chung Lee

Intermediate-length CAG repeats in ATXN2 have been well recognized as a genetic risk factor for amyotrophic lateral sclerosis (ALS). However, the role of similar trinucleotide repeat expansions in the TATA-box binding protein gene (TBP), another disease-associated gene for inherited ataxia, in ALS remains elusive. To assess the association between TBP trinucleotide repeat expansions and ALS, we investigated the repeat lengths in 325 unrelated ALS patients and 1500 controls in the Taiwanese population. The most common size of repeats in the patients and controls were both 36. The repeat lengths ranged from 29 to 46 repeats in the ALS patients and 27 to 43 repeats in the controls. Two ALS patients carried a TBP allele with a repeat number equal or greater than 44 (44 and 46). The patient with the 46 trinucleotide repeats also had a C9ORF72 GGGGCC hexanucleotide repeat expansion. The odds ratio of an individual carrying the CAG/CAA repeats ≥ 44 to have ALS is 23.2 (95% confidence interval: 1.11–484.24; p = 0.04). Our findings suggest that intermediate-length CAG/CAA repeat expansions in TBP may associate with ALS risk.


This work was supported by the grants from Ministry of Science and Technology, Taiwan [107-2314-B-075-014-MY3], Taipei Veterans General Hospital [V109C-060], Taiwan Motor Neuron Disease Association, and Brain Research Center, National Yang-Ming University from the Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) in Taiwan.