Dentatorubral-pallidoluysian atrophy
| Dentatorubral-pallidoluysian atrophy | |
|---|---|
| Classification and external resources | |
| OMIM | 125370 |
| DiseasesDB | 32909 |
| MeSH | D020191 |
| GeneReviews | |
Dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant spinocerebellar degeneration caused by an expansion of a CAG repeat encoding a polyglutamine tract in the atrophin-1 protein. It is also known as Haw River Syndrome and Naito-Oyanagi disease. Although this condition was perhaps first described by Smith et al. in 1958, and several sporadic cases have been reported from Western countries, this disorder seems to be very rare except in Japan.
There are at least eight neurodegenerative diseases that are caused by expanded CAG repeats encoding polyglutamine (polyQ) stretches (see: Trinucleotide repeat disorder). The expanded CAG repeats create an adverse gain-of-function mutation in the gene products. Of these diseases, DRPLA is most similar to Huntington's disease.
DRPLA can be juvenile-onset (< 20 years), early adult-onset (20–40 years), or late adult-onset (> 40 years). Late adult-onset DRPLA is characterized by ataxia, choreoathetosis and dementia. Early adult-onset DRPLA also includes seizures and myoclonus. Juvenile-onset DRPLA presents with ataxia and symptoms consistent with progressive myoclonus epilepsy (myoclonus, multiple seizure types and dementia). Other symptoms that have been described include cervical dystonia, corneal endothelial degenerationautism, and surgery-resistant obstructive sleep apnea.
The human genome contains two atrophin genes; DRPLA has been correlated to the expansion of the polyglutamine region of the atrophin-1 gene on chromosome 12p13.3. A normal number of CAG repeats in the atrophin-1 gene is 7-34, affected individuals display 49-93 repeats. DRPLA displays anticipation, an inverse correlation between the size of the expanded CAG repeat and the age of symptom onset. Paternal transmission results in more prominent anticipation (26–29 years) than maternal transmission (14 to 15 years).
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