Recent progress in spinocerebellar ataxia type-10 (SCA10)

Research output: Contribution to journalReview article

51 Scopus citations

Abstract

Spinocerebellar ataxia type 10 (SCA10) is a dominantly inherited ataxia caused by expansion of ATTCT pentanucleotide repeat in intron 9 of a novel gene, E46L, on chromosome 22q13.3. SCA10 is a complex neurodegenerative condition. Initial studies characterized SCA10 as pure cerebellar ataxia associated with seizures. Recent identification of new SCA10 families revealed more diverse phenotypes, including polyneuropathy, pyramidal signs, cognitive and neuropsychiatric impairment. Moreover, several families manifest with ataxia without seizures. Thus a complete clinical spectrum is emerging. Progress has also been made in understanding the molecular and genetic mechanisms of pathogenesis. The length of expanded ATTCT repeats is variable in different tissues and highly unstable during paternal transmission, revealing complex genetic and pathogenetic processes. Under torsional stress, ATTCT repeats form unpaired DNA structure and may serve as an erroneous DNA replication origin, potentially contributing to repeat instability and aberrant cell cycle entry. E46L is a cytoplasmic protein with unknown function. Reduced expression of E46L in primary neuronal cultures from cerebellum and cortex by small interfering RNAs (siRNAs) caused increased apoptosis, raising the possibility that reduced expression of E46L might also play an important role in SCA10 pathogenesis.

Original languageEnglish (US)
Pages (from-to)37-42
Number of pages6
JournalCerebellum
Volume4
Issue number1
DOIs
StatePublished - 2005

Keywords

  • Anticipation
  • DNA replication
  • Repeat instability
  • Seizure
  • Spinocerebellar ataxia

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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