Molecular basis of heterogeneities of clinical presentation of dentatorubral pallidoluysian atrophy (DRPLA)
Tsuji, S.
Rinsho Shinkeigaku 34(12): 1227-1229
1994
ISSN/ISBN: 0009-918X PMID: 7774119 Document Number: 436743
Dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disorder affecting primarily dentatorubral as well as pallidoluysian atrophy. From a view point of clinical genetics, DRPLA is characterized by prominent anticipation and considerable heterogeneities in its clinical manifestations. Given the fact that unstable CAG repeat expansion is the causative genes for Huntington disease and spinocerebellar ataxia 1, in which anticipation and parental bias of transmission of the severest form are present, we hypothesized that DRPLA might be caused by unstable expansion of a gene containing a CAG repeat. By screening published genes containing CAG repeats, were able to identify the gene for DRPLA located on the chromosome 12. All the DRPLA patients had expanded CAG repeats, and furthermore, there is a good correlation between the degree of CAG repeat expansions and the ages of onset. There are also good correlation in the ages of onset of each of the neurological of manifestations including myoclonus, choreoathetosis, epilepsy, dementia, and psychiatric symptoms. We concluded that the unstable expansion of the CAG repeat in the DRPLA gene is intimately involved in the pathogenesis of DRPLA.