Genetic PrP Prion Diseases

Abstract

Genetic prion diseases (gPrDs) caused by mutations in the prion protein gene () have been classified as genetic Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker disease, or fatal familial insomnia. Mutations in can be missense, nonsense, and/or octapeptide repeat insertions or, possibly, deletions. These mutations can produce diverse clinical features. They may also show varying ancillary testing results and neuropathological findings. Although the majority of gPrDs have a rapid progression with a short survival time of a few months, many also present as ataxic or parkinsonian disorders, which have a slower decline over a few to several years. A few very rare mutations manifest as neuropsychiatric disorders, with systemic symptoms that include gastrointestinal disorders and neuropathy; these forms can progress over years to decades. In this review, we classify gPrDs as rapid, slow, or mixed types based on their typical rate of progression and duration, and we review the broad spectrum of phenotypes manifested by these diseases.

Prion protein glycans reduce intracerebral fibril formation and spongiosis in prion disease

“…In contrast to Alzheimer's disease, amyloid plaques in the brain are rare in prion disease and are often associated with longer disease durations, as observed in Gerstmann-Sträussler-Scheinker disease, for example (3). Prions more commonly form diffuse, synaptic, or punctate aggregates associated with an extraordi- The spongiform degeneration is similar in Prnp 187N mice as compared with WT mice; however, PrP deposits switched from the typical large, dense plaques in WT mice to primarily diffuse aggregates, with occasional rare small plaques in the corpus callosum (lower panel).…”

“…Amyloid plaques accumulate in the brain of patients with Alzheimer's disease and certain familial prion diseases, and are often associated with a clinical course that progresses for more than 3 years (1)(2)(3). In contrast, in sporadic Creutzfeldt-Jakob disease (sCJD), prion aggregates more commonly form diffuse, synaptic, or plaque-like deposits in the brain and symptoms advance with extraordinary rapidity, with a median of 6 months from clinical onset to terminal disease (4)(5)(6).…”

An in vivo 11C‐PK PET study of microglia activation in Fatal Familial Insomnia

“…Genetic prion diseases have been classified as "fast" or "slow" based on the usual clinical course, ranging from very rapid (<3 years of disease duration) to slower courses (>3 years), witnessing a pronounced variability concerning survival time. 4 Therefore, this hypothesis is more likely to hold true in slower, less fulminant, genetic cases.…”

“…2,3 The net majority of the fatal insomnia cases are familial, with FFI qualifying as one of the most common inherited prion disease worldwide. 3 FFI is a rare disease 4 linked to a missense mutation in the prion protein gene (PRNP) at codon-178, with aspartate-asparagine replacement (Asp?Asn) (D178N mutation), 5,6 which has a high, almost complete, penetrance. [5][6][7] The D178N mutation can trigger different clinico-pathological syndromes, either thalamic-dominant FFI or CJD, depending on a ª 2017 The Authors.…”

Rare genetic Creutzfeldt-Jakob disease with E196A mutation: a case report

“…The cellular prion protein (PrP c ) encoded by PRNP is composed of 253 amino acids before post-translation modification, and its mature form is a peptide that is composed of 208 amino acids that is fixed on the cell membrane in a unique way [4]. To date, more than 60 mutations have been identified in the PRNP open reading framework; more than 20 of these mutations are associated with gCJD [5]. The manifestations of gCJD are mainly characterized by rapidly progressive cognitive decline (mainly manifested as memory loss), visual or cerebellar problems, myoclonic jerks, pyramidal or extrapyramidal features, and akinetic mutism [6].…”