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Huntington DiseaseComments

Huntington Disease

Huntington Disease (HD) is an autosomal dominant, late-onset, progressively neurodegenerative disorder caused by mutation of the ubiquitously expressed HD gene. Normal HD alleles have 10 to 26 CAG repeats, while disease HD alleles typically contain more than 36 CAG repeats; 97% of disease alleles are inherited, while 3% of disease alleles are new mutations arising from inherited premutations of 20 to 35 repeats. The function of huntingtin -- the gene product of HD -- is unclear, and it is also unknown how huntingtin encoded by a disease allele leads to the Huntington Disease phenotype.

Age of onset is inversely proportional to the number of CAG repeats in the HD allele. Juvenile onset ensues from over 60 CAG repeats, adult onset ensues from 40-55 CAG repeats and reduced penetrance (possibly no disease phenotype) ensues from 36-41 CAG repeats. Alleles with more than 36 repeats expand during paternal transmission, with somewhat less expansion during maternal transmission. The phenotype includes cognitive loss, behavioral instability and even schizophrenia. As death approaches, motor skills fail such that incontinence and mutism develops; however, behavioral disturbances lessen. The only current treatment for Huntington Disease is pharmacologic treatment of behavioral instability, and lots of support.