Dentatorubral-pallidoluysian atrophy or Naito-Oyanagi disease

Neurogenetics. 1998 Dec;2(1):1-17. doi: 10.1007/s100480050046.

Abstract

Dentatorubral and pallidoluysian atrophy (DRPLA) is an autosomal dominant cerebellar ataxia characterized clinically by myoclonus, epilepsy, cerebellar ataxia, choreoathetosis, and dementia with personality change. Histopathologically, DRPLA is characterized by a unique combination of degenerative changes in both the dentatofugal and the pallidofugal systems. Credit for the establishment of DRPLA as an entity is given to Naito and Oyagagi, who first noticed a strong heritability and an age of onset-dependent variability of the clinical features. Most papers on DRPLA research are written in Japanese, and are extensively reviewed here. After the gene was identified in 1994, DRPLA became known as one of the CAG repeat expansion diseases, in which the responsible gene is located on chromosome 12p and its product is called atrophin-1. Classical genetics revealed that DRPLA shows prominent "anticipation" and modern molecular genetics provided a clear explanation for this phenomenon, by demonstrating a strong instability of the expanded CAG repeat length through generations. The impact of gene analysis of DRPLA on the clinical genetics and neurology are discussed. Moreover, possible mechanism(s) underlying the neuronal cell death in DRPLA are discussed in terms of the molecular pathology.

Publication types

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

MeSH terms

  • Atrophy
  • Brain / pathology
  • Chromosome Mapping
  • Chromosomes, Human, Pair 12
  • Humans
  • Japan
  • Myoclonic Epilepsies, Progressive / genetics*
  • Myoclonic Epilepsies, Progressive / pathology
  • Myoclonic Epilepsies, Progressive / physiopathology
  • Nerve Tissue Proteins / genetics*
  • Trinucleotide Repeats

Substances

  • Nerve Tissue Proteins
  • atrophin-1