Dentatorubral-pallidoluysian atrophy (DRPLA). Molecular basis for wide clinical features of DRPLA

Clin Neurosci. 1995;3(1):23-7.

Abstract

Dentatorubral-pallidoluysian atrophy (DRPLA) is a rare autosomal dominant neurodegenerative disorder characterized clinically by various combinations of myoclonus, epilepsy, cerebellar ataxia, choreoathetosis, dementia and psychiatric symptoms. Based on the phenomenon of anticipation, the gene for DRPLA was recently identified. DRPLA is caused by unstable expansion of a CAG repeat in the gene located on the short arm of chromosome 12. As have been observed in Huntington's disease and SCA1, there is a strong correlation between the age of onset and the size of CAG repeats. Furthermore, patients with larger repeats tend to show a PME (progressive myoclonus epilepsy) phenotype as well as earlier ages of onset. More prominent anticipation and larger intergenerational increase of CAG repeats in paternal transmission can be accounted for by the meiotic instability of CAG repeats in male gametogenesis. Comparison of size distributions of CAG repeats in Japanese, African-American and white populations revealed that 7.4% of the Japanese alleles had greater than 19 repeats, whereas none of the whites and 1% of the African-American alleles were of this size. The results may account for the ethnic predilection of DRPLA.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age of Onset
  • Atrophy
  • Cerebellar Ataxia / diagnosis
  • Cerebellar Ataxia / genetics*
  • Cerebellar Nuclei / pathology*
  • Female
  • Globus Pallidus / pathology*
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Phenotype
  • Red Nucleus / pathology*
  • Repetitive Sequences, Nucleic Acid
  • Spinocerebellar Degenerations / genetics