Huntington's disease-like 2

Russell L. Margolis, Susan E. Holmes, Dobrila D. Rudnicki, Elizabeth O'Hearn, Christopher A. Ross, Olga Pletnikova, Juan C. Troncoso

Research output: Chapter in Book/Report/Conference proceedingChapter


Huntington's disease-like 2 (HDL2) is a rare autosomal dominant adult-onset progressive neurodegenerative disorder. Clinically and pathologically, HDL2 is nearly indistinguishable from Huntington's disease (HD), and is characterized like HD by selective striatal degeneration and neuronal intranuclear inclusions. Like HD, the cause of HDL2 is an expansion of a polymorphic CAG/CTG repeat expansion with the threshold for disease at about 40 triplets. The HDL2 repeat is located on chromosome 16q24.3 in a variably spliced exon of the gene junctophilin-3 (JPH3). Unlike HD, the HDL2 repeat does not encode polyglutamine, but instead is variably inframe to encode polyalanine or polyleucine, or falls within the 3' untranslated region (UTR). The mechanism by which the HDL2 expansion mutation leads to nearly the same phenotype as the HD polyglutamine expansion is unknown, but may have similarities to that of myotonic dystrophy types 1 and 2. The availability of HDL2 brain tissue and the development of cell and animal models of HDL2 should facilitate elucidation of the pathogenesis of HDL2, and perhaps, in the process, lead to insights into HD and DM.

Original languageEnglish (US)
Title of host publicationGenetic Instabilities and Neurological Diseases, Second Edition
PublisherElsevier Inc.
Number of pages13
ISBN (Print)9780123694621
StatePublished - 2006

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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