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DRPLA is a progressive neurodegenerative disease presenting with cerebellar ataxia, myoclonic epilepsy, choreoathetosis and - with disease progression - dementia. If the choreoathetotische symtptoms are more prominent, clinical delineation from Huntington’s disease may be difficult. DRPLA is fairly common in Japan (up to 20% of all hereditary ataxias), but it is very rare in Europe.
Similar to Huntington’s disease and most SCAs DRPLA belongs to the group of polyglutamine diseases. It is caused by a pathological expansion of a polymorphic CAG repeat in the coding region of the DRPLA (B37) gene on chromosome 12p13.31. Normal alleles comprise up to 36 CAGs whereas disease causing allele contain 49 to 88 CAGs. Accordingly in mutation carriers the polyglutamine stretch within the atrophin 1 protein is expanded pathologically. There is no overlap between normal and pathological CAG numbers. The mode of inheritance is autosomal dominant and there is evidence for reduced penetrance in some cases. Anticipation phenomena are perhaps more frequent than in other polyglutamine diseases, and they occur predominantly with paternal transmission. Disease onset and course can be quite variable, and they are in part depending on the length of the CAG stretch. Specific therapeutic strategies are not yet available.Identical expansions of the DRPLA CAG stretch are observed in Haw-River-syndrome which is clinically distinguishable from DRPLA by the absence of epileptic features. Neuropathologically pronounced subcortical demyelination and calcification of the basal ganglia is observed.
Dr. med. S. Wieczorek
Humangenetik
Gebäude MA 5
Ruhr-Universität
Universitätsstr. 150
44801 Bochum
GermanyTel.: +49 234 32 23831
Fax: +49 234 32 14196
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