Trinucleotide repeat expansion of TATA-binding protein gene associated with Parkinson's disease: A Thai multicenter study

Abstract Introduction Spinocerebellar ataxia type 17 (SCA17) is an inherited cerebellar degeneration associated with trinucleotide repeat expansions in the TATA-binding protein gene ( TBP ). Low-range expansions of TBP have recently been described in association with Parkinson's disease (PD). However, these low-range expansion alleles were also observed in healthy individuals. Prior distinct findings may result from reduced penetrance or age-dependent susceptibility, which may influence phenotypic expression. Methods A case-control study of 456 PD patients and 374 control subjects was conducted. Data and blood samples were collected during 2008–2013. Control subjects were individuals over 65 years old without parkinsonism. Sizes of TBP trinucleotide repeats were analyzed. All available carriers of the TBP repeat of ≥40 repeats were re-examined. Results A high prevalence of carriers of TBP repeat expansion ≥41 developed PD, mainly at an advanced age. Half of these carriers had onset after 70 years of age (range 34–84). Seven participants carried expansion alleles of ≥42, and all had PD. Fourteen participants (six patients and eight controls) carried a heterozygous 41-repeat allele. At the current mean age of 79 years and mean follow-up period of 4 years, three out of the eight control carriers of the 41-repeat allele developed PD, while none of the thirteen asymptomatic carriers of the 40-repeat allele did. Conclusions A high prevalence of PD was observed in carriers of low-range expansions of TBP (41–45 repeats), especially in elderly. This finding suggests that cut-off value for pathological TBP repeat expansion appear to be 41.