Introduction

Dentatorubral-pallidoluysian atrophy (DRPLA) is a rare, autosomal dominant, neurodegenerative disorder clinically characterized by various combinations of cerebellar ataxia, choreoathetosis, myoclonus, epilepsy, dementia, and psychiatric symptoms (MIM# 125370) (Naito and Oyanagi, 1982). The term DRPLA was originally used by Smith et al. to describe a neuropathological condition associated with severe neuronal loss, particularly in the dentatorubral and pallidoluysian systems of the central nervous system, in a sporadic case without a family history (Smith et al., 1958; Smith, 1975). The hereditary form of DRPLA was first described in 1972 by Naito and his colleagues. Since then, several reports on Japanese pedigrees with similar clinical presentations have been published (Oyanagi and Naito, 1977; Tanaka et al., 1977; Hirayama et al., 1981; Iizuka et al., 1984; Suzuki et al., 1985; Iizuka and Hirayama, 1986; Akashi et al., 1987; Iwabuchi, 1987; Iwabuchi et al., 1987; Naito et al., 1987), and DRPLA has been established as a distinct disease entity.

The gene for DRPLA was discovered by two independent Japanese groups in 1994, and an unstable CAG trinucleotide repeat expansion in the protein-coding region of this gene was found to be the causative mutation for DRPLA (Koide et al., 1994; Nagafuchi et al., 1994a).