“What’s next for genomics and prion diseases?”


Prions are transmissible agents composed of aggregates of misfolded cellular prion protein (PrP) that cause fatal neurodegenerative diseases. It is increasingly recognized that the mechanism of seeded propagation of aggregates of misfolded proteins is a fundamental molecular process that is common to all of the major human neurodegenerative diseases [1]. Prion diseases arise in one of three ways: via inherited, acquired or sporadic (unknown) causes. Inherited prion disease is associated with mutations in the coding sequence of the prion protein gene (PRNP), which lead to misfolding of PrP. More than 30 such mutations have been described to date. Sporadic Creutzfeldt–Jakob disease (CJD) is the most common form of the disease in humans and occurs at an annual incidence of approximately one per million. The initial prompt that sets in motion PrP misfolding is unknown in these cases and may either represent a random event or reflect a somatic mutation in one or more brain cells. Acquired prion diseases include variant CJD (vCJD) that is likely caused by zoonotic transmission via ingestion of foods contaminated with bovine spongiform encephalopathy. Other examples are iatrogenic transmission occurring accidently during medical procedures such as dura mater transplantation or cadaver-derived growth hormone therapy, as well as the human disease kuru that was restricted to isolated populations in Papua New Guinea where the disease was acquired through ritualistic endocannibalism. All types of prion disease are highly heterogeneous in terms of their clinical presentation, the age of onset and in the case of acquired disease, the incubation time.

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