Instituto Valenciano de Microbiología

Masía El Romeral
Ctra. de Bétera a San Antonio Km. 0.3
46117 Bétera (Valencia)
Phone. 96 169 17 02
Fax 96 169 16 37
CIF B-96337217


Prion, Disease ... (Prion disease: Creutzfeldt-Jakob disease -CJD-, Gerstmann-Straussler-Scheinker syndrome -GSS-, and fatal familial insomnia -FFI-) - Gen PRNP.

Prion disease represents a group of diseases that affect the nervous system in humans and animals. In people, these diseases alter brain function, causing memory changes, personality and behavior, dementia and abnormal movements, especially ataxia. Signs and symptoms of prion disease usually begin in adulthood and worsen over time, leading to death within a few months or a few years. This group of diseases includes family Creutzfeldt-Jakob disease (CJD), the Gerstmann-Sträussler-Scheinker syndrome (GSS), and fatal familial insomnia (FFI).

Between 10 and 15 percent of all cases of disease are caused by mutations in the PRNP gene. The other 85 to 90 percent of cases of prion disease are classified as sporadic or acquired. People with sporadic disease have no family history of the disease, or an identified mutation in the PRNP gene. Sporadic forms of prion disease including Creutzfeldt-Jakob sporadic (sCJD), sporadic fatal insomnia (SFI), and a variably sensitive to protease (VPSPr). The acquired form of prion diseases resulting from exposure to PrPSc from an external source. For example, the variant of Creutzfeldt-Jakob disease (vCJD) is a type of prion disease acquired by ingesting meat products from cattle containing PrPSc by the disease. In cows, this form of the disease known as bovine spongiform encephalopathy (BSE) or, more commonly, the "mad cow disease". Another example of transmitting the acquired when people ate human tissues affected during the cannibalistic funeral rites. Rarely, prion disease can be transmitted through accidental exposure to contaminated PrPSc tissue during a medical procedure. This type of disease, accounting for 1 to 2 percent of all cases, is classified as iatrogenic.

The PRNP gene, located on the short arm of chromosome 20 (20p13), encoding the prion protein -prión- (PrP) which is active in the brain and other tissues. Although the precise function of this protein is unknown, is believed to play a role in copper transport in cells, the protection of neurons against injury and communication between neurons.

They have identified more than 30 mutations in the PRNP gene in individuals with familial forms of prion disease including Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler-Scheinker (GSS), and insomnia fatal familial (FFI). In familial forms of the disease, mutations resulting in the synthesis of a protein abnormally (PrPSc), from a copy of the gene. The abnormal protein accumulates in the brain, resulting in the formation of clumps that damage or destroy neurons. The loss of these cells creates vacuoles in the brain, leading to the signs and symptoms of the disease.

Several polymorphisms have been identified in the PRNP gene affecting the individual amino acids in PrP. These polymorphisms do not cause prion disease, but may increase the risk of developing the disorder. Studies have focused on the effects of a polymorphism at position 129 of PrP (Met129Val or M129V). In this position, people can have the amino acid methionine (Met) or the amino acid valine (Val). Because people inherit a copy of the PRNP gene from each parent, at position 129 of an individual can receive methionine from both parents (Met / Met), valine both parents (Val / Val), or methionine from one parents and other valine (Met / Val). The Met129Val polymorphism appears to influence the risk of developing the disease by prions. Most affected individuals have the same amino acid at position 129 (Met / Met or Val / Val) instead of different amino acids (Met / Val). Having Met / Met at position 129 it is also associated with an earlier age of onset and a more rapid deterioration of the signs and symptoms of the disease.

Familial forms of prion disease is inherited as an autosomal dominant, which means that a copy of the altered gene PRNP in each cell is sufficient to cause the alteration. In most cases, an affected person inherits the altered gene from an affected parent. In some people, familial forms of prion disease are caused by a new mutation in the gene that occurs during the formation of reproductive cells parents or early embryonic development. Although these people do not have an affected parent, they can transmit genetic change their children. Sporadic and acquired forms are not inherited.  

Tests in IVAMI: in IVAMI perform detection of mutations associated with prion disease by the complete PCR amplification of the exons of the PRNP gene, and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).