A disorder similar to Huntington's disease is associated with a novel CAG repeat expansion

Russell Louis Margolis, Elizabeth O'Hearn, Adam Rosenblatt, Virginia Willour, Susan E. Holmes, Mary L. Franz, Colleen Callahan, Hyon S. Hwang, Juan C Troncoso, Christopher A Ross

Research output: Contribution to journalArticle

Abstract

Huntington's disease (HD) is an autosomal dominant disorder characterized by abnormalities of movement, cognition, and emotion and selective atrophy of the striatum and cerebral cortex. While the etiology of HD is known to be a CAG trinucleotide repeat expansion, the pathways by which this mutation causes HD pathology remain unclear. We now report a large pedigree with an autosomal dominant disorder that is clinically similar to HD and that arises from a different CAG expansion mutation. The disorder is characterized by onset in the fourth decade, involuntary movements and abnormalities of voluntary movement, psychiatric symptoms, weight loss, dementia, and a relentless course with death about 20 years after disease onset. Brain magnetic resonance imaging scans and an autopsy revealed marked striatal atrophy and moderate cortical atrophy, with striatal neurodegeneration in a dorsal to ventral gradient and occasional intranuclear inclusions. All tested affected individuals, and no tested unaffecteds, have a CAG trinucleotide repeat expansion of 50 to 60 triplets, as determined by the repeat expansion detection assay. Tests for the HD expansion, for all other known CAG expansion mutations, and for linkage to chromosomes 20p and 4p were negative, indicating that this mutation is novel. Cloning the causative CAG expansion mutation for this new disease, which we have termed Huntington's disease-like 2, may yield valuable insight into the pathogenesis of HD and related disorders.

Original languageEnglish (US)
Pages (from-to)373-380
Number of pages8
JournalAnnals of Neurology
Volume50
Issue number3
DOIs
StatePublished - 2001

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Huntington Disease
Mutation
Trinucleotide Repeat Expansion
Atrophy
Corpus Striatum
Intranuclear Inclusion Bodies
Dyskinesias
Pedigree
Cerebral Cortex
Cognition
Psychiatry
Dementia
Organism Cloning
Weight Loss
Autopsy
Emotions
Chromosomes
Magnetic Resonance Imaging
Pathology
Brain

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

A disorder similar to Huntington's disease is associated with a novel CAG repeat expansion. / Margolis, Russell Louis; O'Hearn, Elizabeth; Rosenblatt, Adam; Willour, Virginia; Holmes, Susan E.; Franz, Mary L.; Callahan, Colleen; Hwang, Hyon S.; Troncoso, Juan C; Ross, Christopher A.

In: Annals of Neurology, Vol. 50, No. 3, 2001, p. 373-380.

Research output: Contribution to journalArticle

Margolis, RL, O'Hearn, E, Rosenblatt, A, Willour, V, Holmes, SE, Franz, ML, Callahan, C, Hwang, HS, Troncoso, JC & Ross, CA 2001, 'A disorder similar to Huntington's disease is associated with a novel CAG repeat expansion', Annals of Neurology, vol. 50, no. 3, pp. 373-380. https://doi.org/10.1002/ana.1124
Margolis, Russell Louis ; O'Hearn, Elizabeth ; Rosenblatt, Adam ; Willour, Virginia ; Holmes, Susan E. ; Franz, Mary L. ; Callahan, Colleen ; Hwang, Hyon S. ; Troncoso, Juan C ; Ross, Christopher A. / A disorder similar to Huntington's disease is associated with a novel CAG repeat expansion. In: Annals of Neurology. 2001 ; Vol. 50, No. 3. pp. 373-380.
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