Although prion diseases are generally thought to present as rapidly progressive 
dementias with survival of only a few months, the phenotypic spectrum for 
genetic prion diseases (gPrDs) is much broader. The majority have a rapid 
decline with short survival, but many patients with gPrDs present as slowly 
progressive ataxic or parkinsonian disorders with progression over a few to 
several years. A few very rare mutations even present as neuropsychiatric 
disorders, sometimes with systemic symptoms such as gastrointestinal disorders 
and neuropathy, progressing over years to decades. gPrDs are caused by mutations 
in the prion protein gene (PRNP), and have been historically classified based on 
their clinicopathological features as genetic Jakob-Creutzfeldt disease (gJCD), 
Gerstmann-Sträussler-Scheinker (GSS), or Fatal Familial Insomnia (FFI). 
Mutations in PRNP can be missense, nonsense, and octapeptide repeat insertions 
or a deletion, and present with diverse clinical features, sensitivities of 
ancillary testing, and neuropathological findings. We present the UCSF gPrD 
cohort, including 129 symptomatic patients referred to and/or seen at UCSF 
between 2001 and 2016, and compare the clinical features of the gPrDs from 22 
mutations identified in our cohort with data from the literature, as well as 
perform a literature review on most other mutations not represented in our 
cohort. E200K is the most common mutation worldwide, is associated with gJCD, 
and was the most common in the UCSF cohort. Among the GSS-associated mutations, 
P102L is the most commonly reported and was also the most common at UCSF. We 
also had several octapeptide repeat insertions (OPRI), a rare nonsense mutation 
(Q160X), and three novel mutations (K194E, E200G, and A224V) in our UCSF cohort. 
© 2016 Wiley Periodicals, Inc.