Pathological repeat variation at the SCA17/TBP gene in south Indian patients

Lone, Waseem; Khan, Imran Ali; Shaik, Noor Ahmad; Meena, A K; Rao, K. Prabhakar; Hasan, Qurratulain

doi:10.1016/j.jns.2015.07.044

Cited by 1 publication

(1 citation statement)

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“…(1) 338/346 (97.7%) ATX-TBP patients had ≥41 repeats (8 patients with 33, 34, or 38 repeats that lacked the typical above-mentioned ATX-TBP phenotypic characteristics were all reported in a single article, 21 and an alternative cause of genetic ataxia cannot be ruled out); ( 2) almost all patients with PD (11,742/11,757, 99.9%) and healthy individuals (16,748/16,759, 99.9%) had ≤42 repeats in the TBP gene; and (3) there is a gray zone between 41 and 45 repeats with RP, because 64/12,845 (0.5%) healthy subjects were reported within this range of repeats. In other words, in the data we extracted, we found no firm evidence of TBP-related disease in those with repeats of ≤40, and no healthy subjects with repeats greater than 45.…”

Section: Resultsmentioning

confidence: 99%

Genotype–Phenotype Correlations for ATX‐TBP (SCA17): MDSGene Systematic Review

et al. 2022

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A BS TRACT: Spinocerebellar ataxia type 17 or ATX-TBP is a CAG/CAA repeat expansion disorder characterized by marked clinical heterogeneity. Reports of affected carriers with subthreshold repeat expansions and of patients with Parkinson's disease (PD) with expanded repeats have cast doubt on the established cutoff values of the expansions and the phenotypic spectrum of this disorder. The objective of this systematic review was to explore the genotype-phenotype relationships for repeat expansions in TBP to delineate the ATX-TBP phenotype and reevaluate the pathological range of repeat expansions. The International Parkinson and Movement Disorder Society Genetic Mutation Database (MDSGene) standardized data extraction protocol was followed. Clinically affected carriers of reported ATX-TBP expansions were included. Publications that contained repeat sizes in screened cohorts of patients with PD and/or healthy individuals were included for a separate evaluation of cutoff values. Phenotypic and genotypic data for 346 ATX-TBP patients were curated. Overall, 97.7% of the patients had ≥41 repeats, while 99.6% of patients with PD and 99.9% of healthy individuals had ≤42 repeats, with a gray zone of reduced penetrance between 41 and 45 repeats. Pure parkinsonism was more common in ATX-TBP patients with 41 to 45 repeats than in the group with ≥46 repeats, which conversely more often presented with a complex phenotype with mixed movement disorders. An updated genotype-phenotype assessment for ATX-TBP is provided, and new repeat expansion cutoff values of reduced penetrance (41-45 expanded repeats) and full penetrance (46-66 expanded repeats) are proposed. These adjusted cutoff values will have diagnostic and counseling implications and may guide future clinical trial

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Section: Resultsmentioning

confidence: 99%