Evaluation of various movement disorders in patients of genetically proven Spino Cerebellar Ataxia: A study from a tertiary care center in Northern India

Radhakrishnan, Divya M.; Goyal, Vinay; Srivastava, Abhilekh; Behari, Madhuri; Shukla, Geeta

doi:10.1016/j.parkreldis.2017.11.076

Cited by 2 publications

(6 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1,2 To date, at least 50 genetic loci have been reported to be associated with SCA subtypes. 1,[3][4][5][6][7][8] The CAG repeat expansions encode for a polyglutamine (polyQ) stretch underlying the polyQ diseases, 9,10 the polyQ SCAs of which account for the most frequent SCA subtypes. However, over the last two decades, no additional neurodegenerative ataxia has been qualified as polyQ disease.…”

mentioning

confidence: 99%

“…Spinocerebellar ataxias (SCAs) are a group of autosomal dominant neurodegenerative disorders that typically present with cerebellar ataxia and variable nonataxic symptoms 1,2 . To date, at least 50 genetic loci have been reported to be associated with SCA subtypes 1,3‐8 . The CAG repeat expansions encode for a polyglutamine (polyQ) stretch underlying the polyQ diseases, 9,10 the polyQ SCAs of which account for the most frequent SCA subtypes.…”

mentioning

confidence: 99%

See 1 more Smart Citation

CAG Repeat Expansion in THAP11 Is Associated with a Novel Spinocerebellar Ataxia

et al. 2023

View full text Add to dashboard Cite

Background More than 50 loci are associated with spinocerebellar ataxia (SCA), and the most frequent subtypes share nucleotide repeats expansion, especially CAG expansion. Objective The objective of this study was to confirm a novel SCA subtype caused by CAG expansion. Methods We performed long‐read whole‐genome sequencing combined with linkage analysis in a five‐generation Chinese family, and the finding was validated in another pedigree. The three‐dimensional structure and function of THAP11 mutant protein were predicted. Polyglutamine (polyQ) toxicity of THAP11 gene with CAG expansion was assessed in skin fibroblasts of patients, human embryonic kidney 293 and Neuro‐2a cells. Results We identified THAP11 as the novel causative SCA gene with CAG repeats ranging from 45 to 100 in patients with ataxia and from 20 to 38 in healthy control subjects. Among the patients, the number of CAA interruptions within CAG repeats was decreased to 3 (up to 5–6 in controls), whereas the number of 3′ pure CAG repeats was up to 32 to 87 (4–16 in controls), suggesting that the toxicity of polyQ protein was length dependent on the pure CAG repeats. Intracellular aggregates were observed in cultured skin fibroblasts from patients. THAP11 polyQ protein was more intensely distributed in the cytoplasm of cultured skin fibroblasts from patients, which was replicated with in vitro cultured neuro‐2a transfected with 54 or 100 CAG repeats. Conclusions This study identified a novel SCA subtype caused by intragenic CAG repeat expansion in THAP11 with intracellular aggregation of THAP11 polyQ protein. Our findings extended the spectrum of polyQ diseases and offered a new perspective in understanding polyQ‐mediated toxic aggregation. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

show abstract

mentioning

confidence: 99%

mentioning

confidence: 99%

CAG Repeat Expansion in THAP11 Is Associated with a Novel Spinocerebellar Ataxia

et al. 2023

View full text Add to dashboard Cite

show abstract

“…A tremor prevalence of 30–50% in SCA2 was also noted in other studies [ 11 13 14 15 16 17 ]. However, some reports documented considerably lower [ 18 19 20 21 22 ], or higher rates of tremor [ 7 23 ]. Tremor in SCA2 was found to be associated with a longer duration of disease [ 12 ], larger CAG repeat expansion [ 16 ], and faster progression [ 11 ].…”

Section: Classification Of Scamentioning

confidence: 99%

“…Tremor in SCA2 was found to be associated with a longer duration of disease [ 12 ], larger CAG repeat expansion [ 16 ], and faster progression [ 11 ]. Postural or intention tremor is more common than rest tremor in SCA2 [ 13 14 16 17 18 19 21 ]. Regarding rest tremor in SCA2, some studies note scarcity [ 13 20 24 ], while others document it more consistently, often with a parkinsonian phenotype [ 7 9 , 18 25 26 27 28 ].…”

Section: Classification Of Scamentioning

confidence: 99%