Genetic prion disease caused by PRNP Q160X mutation presenting with an orbitofrontal syndrome, cyclic diarrhea, and peripheral neuropathy

Jamie C. Fong, Julio C. Rojas, Jee Bang, Andrea Legati, Katherine P. Rankin, Sven Forner, Zachary A. Miller, Anna M. Karydas, Giovanni Coppola, Carrie K. Grouse, Jeffrey Ralph, Bruce L. Miller, Michael D. Geschwind

Research output: Contribution to journalArticle

Abstract

Patients with pathogenic truncating mutations in the prion gene (PRNP) usually present with prolonged disease courses with severe neurofibrillary tangle and cerebral amyloidosis pathology, but more atypical phenotypes also occur, including those with dysautonomia and peripheral neuropathy. We describe the neurological, cognitive, neuroimaging, and electrophysiological features of a 31-year-old man presenting with an orbitofrontal syndrome, gastrointestinal symptoms, and peripheral neuropathy associated with PRNP Q160X nonsense mutation, with symptom onset at age 27. The mutation was also detected in his asymptomatic father and a symptomatic paternal cousin; several members of prior generations died from early onset dementia. This is the first report of a family affected with the nonsense PRNP mutation Q160X displaying clear autosomal dominant disease in multiple family members and reduced penetrance. This case strengthens the evidence suggesting an association between PRNP truncating mutations and prion systemic amyloidosis. PRNP gene testing should be considered in any patient with atypical dementia, especially with early onset and neuropathy, even in the absence of a family history.

Original languageEnglish (US)
Pages (from-to)249-258
Number of pages10
JournalJournal of Alzheimer's Disease
Volume55
Issue number1
DOIs
StatePublished - 2016
Externally publishedYes

Keywords

  • Amyloidosis
  • DNA sequencing
  • dysautonomia
  • exome
  • mutation
  • peripheral neuropathy
  • prion dementia

ASJC Scopus subject areas

  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

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  • Cite this

    Fong, J. C., Rojas, J. C., Bang, J., Legati, A., Rankin, K. P., Forner, S., Miller, Z. A., Karydas, A. M., Coppola, G., Grouse, C. K., Ralph, J., Miller, B. L., & Geschwind, M. D. (2016). Genetic prion disease caused by PRNP Q160X mutation presenting with an orbitofrontal syndrome, cyclic diarrhea, and peripheral neuropathy. Journal of Alzheimer's Disease, 55(1), 249-258. https://doi.org/10.3233/JAD-160300