Dentatorubral-pallidoluysian atrophy (DRPLA): Model for Huntington's disease and other polyglutamine diseases

First description and historical review Dentatorubral-pallidoluysian atrophy (DRPLA) was first reported by J. K. Smith in 1958, in a detailed clinical description of a single case (Smith et al., 1958). The disorder is rare in the western hemisphere, but in Japan is approximately as prevalent as Huntington's disease (HD). Like HD, DRPLA is inherited as an autosomal dominant, and shows a wide range of age of onset, with anticipation caused by instability of the triplet repeat expansion (Naito & Oyanagi, 1982; Takahashi et al., 1988; Iizuka et al., 1984; Goto et al., 1982). The triplet repeat expansion mutation which causes DRPLA was identified as part of a program to find genes with triplet repeats as candidates for neuropsychiatric disorders with anticipation (Li et al., 1993; Ross et al., 1993). Two Japanese groups independently used the primers for amplifying the CAG repeat to determine that it is expanded in DRPLA and identify the gene in which this expanded repeat is located, termed atrophin-1 (Koide et al., 1994; Nagafuchi et al., 1994; Margolis et al., 1996). The availability of a genetic test for DRPLA then made it possible to identify other families with DRPLA, some of whom had previously been diagnosed as having HD.Morphological pattern of pathology Among the polyglutamine neurodegenerative diseases, the pathology of DRPLA is most similar to that of HD (Ross, 1995). The areas most severely affected are given in the name of the disease. The dentate nucleus of the cerebellum has the greatest degeneration.