Genetic and clinical analyses of spinocerebellar ataxia type 8 in mainland China

J Neurol. 2019 Dec;266(12):2979-2986. doi: 10.1007/s00415-019-09519-2. Epub 2019 Aug 30.

Abstract

Background: Spinocerebellar ataxia type 8 (SCA8) is a rare autosomal dominant neurodegenerative disease caused by CTA/CTG repeat expansion in the ATXN8/ATXN8OS gene.

Methods: To analyze the frequency and clinical characteristics of SCA8 patients in mainland China, we combined polymerase chain reaction (PCR) and triplet repeat-primed PCR (TRP-PCR) to detect the CTA/CTG expansion. We studied a cohort of 362 ataxia patients in which the other known causative genes had been previously excluded, from among 1294 index patients. Positive samples were validated by southern blotting.

Results: The CTA/CTG expansion was observed in six probands, accounting for approximately 0.46% (6/1294) in all patients, and 1.66% (6/362) in patients without definite molecular diagnosis. Clinically, aside from the typical SCA8 phenotype, some patients carrying the CTA/CTG expansion exhibited the cerebellar form of multisystem atrophy (MSA-C) and ataxia with paroxysmal kinesigenic dyskinesia (PKD).

Conclusion: For the first time, we described the PKD phenotype in association with CTA/CTG expansion, suggesting that CTA/CTG expansion might play a role in the pathogenesis of paroxysmal dyskinesia symptoms.

Keywords: ATXN8/ATXN8OS; Cerebellar form of multisystem atrophy (MSA-C); Paroxysmal kinesigenic dyskinesia (PKD); Spinocerebellar ataxia type 8 (SCA8); Trinucleotide repeat expansion.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Child
  • China
  • Cohort Studies
  • Dyskinesias / etiology
  • Dyskinesias / genetics*
  • Dyskinesias / physiopathology*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Phenotype
  • Spinocerebellar Degenerations / complications
  • Spinocerebellar Degenerations / genetics*
  • Spinocerebellar Degenerations / physiopathology*
  • Trinucleotide Repeat Expansion / genetics*
  • Young Adult

Supplementary concepts

  • Spinocerebellar ataxia 8