Genetics Mutations in the PRNP gene cause prion disease. Familial forms of prion disease are caused by inherited mutations in the PRNP gene. Only a small percentage of all cases of prion disease run in families, however. Most cases of prion disease are sporadic, which means they occur in people without any known risk factors or gene mutations. In rare circumstances, prion diseases also can be transmitted by exposure to prion-contaminated tissues or other biological materials obtained from individuals with prion disease. The PRNP gene provides the instructions to make a protein called the prion protein (PrP). Under normal circumstances, this protein may be involved in transporting copper into cells. It may also be involved in protecting brain cells and helping them communicate. 24 Point-Mutations in this gene cause cells to produce an abnormal form of the prion protein, known as PrPSc. This abnormal protein builds up in the brain and destroys nerve cells, resulting in the signs and symptoms of prion disease. Familial forms of prion disease are inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person inherits the altered gene from one affected parent. In some people, familial forms of prion disease are caused by a new mutation in the PRNP gene. Although such people most likely do not have an affected parent, they can pass the genetic change to their children. Protein-only hypothesis Protein could be the infectious agent, inducing its own replication by causing conformational change of normal cellular PrPC into PrPSc. Evidence for this hypothesis: :*Infectivity titre correlates with PrPSc levels. However, this is disputed. :*PrPSc is an isomer of PrPC :*Denaturing PrP removes infectivity ;*PrP-null mice cannot be infected ;*PrPC depletion in the neural system of mice with established neuroinvasive prion infection reverses early spongeosis and behavioural deficits, halts further disease progression and increases life-span Multi-component hypothesis While not containing a nucleic acid genome, prions may be composed of more than just a protein. Purified PrPC appears unable to convert to the infectious PrPSc form, unless other components are added, such as RNA and lipids. These other components, termed cofactors, may form part of the infectious prion, or they may serve as catalysts for the replication of a protein-only prion. Spiroplasma hypothesis There is some disputed evidence for the role of bacteria of the Spiroplasma genus in the etiology of<unk> s, primarily due to the work of Frank Bastian. The fact that PrPSc cannot be detected in about 10% of cases of CWD, while Bastian claims to have successfully cultured Spiroplasma spp. from the brains of 100% of deer with CWD and sheep with scrapie, which were able to spread the disease to other ruminants in the absence of PrPSc, has led him and others to suspect that Spiroplasma infection may be the genuine cause of<unk> s. Under this hypothesis PrPSc would merely be an imperfect marker of infection (with both sensitivity and NPV Sc :*An increasing titre of PrPSc as the disease progresses suggests a replicating agent.
Transmissible spongiform encephalopathy
Fatal insomnia
Variant Creutzfeldt–Jakob disease
Bovine spongiform encephalopathy
Powassan encephalitis
Camel spongiform encephalopathy
Hashimoto's encephalopathy
Viliuisk encephalomyelitis