Affiliations: [a] Department of Neurology, Memory and Aging Center, University of California, San Francisco, CA, USA
| [b] Departments of Psychiatry and Neurology, University of California, Los Angeles, CA, USA
| [c] Department of Neurology, Spine & Nerve EMG Unit, University of California, San Francisco, CA, USA
Correspondence:
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Correspondence to: Michael D. Geschwind, MD, PhD,University of California, San Francisco (UCSF), Memory and Aging Center, Box 1207, San Francisco, CA 94143-1207, USA. Tel.: +1 415 476 2901; Fax: +1 415 476 0213; E-mail: [email protected].
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.
