Prion diseases can be hereditary, but not all prion diseases are inherited. Some prion diseases arise spontaneously or are acquired through infection, while others result from mutations in the prion protein gene (*PRNP*), making them hereditary.
Prion diseases are caused by misfolded prion proteins (PrP^Sc^), which accumulate in the brain and cause neurodegeneration. The normal prion protein (PrP^C^) is encoded by the *PRNP* gene located on chromosome 20. Mutations in this gene can lead to inherited prion diseases, which are passed down in families in an autosomal dominant manner, meaning only one copy of the mutated gene is sufficient to cause disease[1][4].
**Hereditary prion diseases include:**
– **Fatal Familial Insomnia (FFI):** This rare disease is caused by a specific mutation at codon 178 of the *PRNP* gene, combined with a methionine at position 129. It leads to severe thalamic degeneration and progressive insomnia. FFI is autosomal dominant and hereditary[1].
– **Gerstmann-Sträussler-Scheinker (GSS) Disease:** GSS is also inherited in an autosomal dominant pattern. The most common mutation is P102L in the *PRNP* gene, but many other variants exist. GSS has almost complete penetrance, meaning nearly all individuals with the mutation will develop the disease[2].
– **Familial Creutzfeldt-Jakob Disease (fCJD):** About 5-10% of CJD cases are hereditary, caused by mutations in the *PRNP* gene. These mutations lead to abnormal prion protein folding and disease. fCJD differs from sporadic and acquired forms of CJD, which are not inherited[3].
**Non-hereditary prion diseases:**
– **Sporadic CJD:** The most common form, believed to arise spontaneously due to a random misfolding of the prion protein without any genetic mutation or infection[3].
– **Acquired prion diseases:** These occur through exposure to infectious prions, such as variant CJD from eating BSE-contaminated beef or kuru from ritualistic cannibalism. These are not hereditary but transmitted by direct exposure to infected tissue[2][3][5].
**Genetics and inheritance:**
The *PRNP* gene mutations causing hereditary prion diseases are autosomal dominant, so a child of an affected parent has a 50% chance of inheriting the mutation. The mutations alter the amino acid sequence of the prion protein, causing it to misfold and accumulate in the brain, leading to neurodegeneration[1][2][4].
**Key points about hereditary prion diseases:**
– They are rare but uniformly fatal neurodegenerative disorders.
– Caused by specific mutations in the *PRNP* gene.
– Inherited in an autosomal dominant pattern.
– Show high penetrance, meaning carriers almost always develop disease.
– Symptoms and disease progression vary depending on the mutation.
– Diagnosis often involves genetic testing for *PRNP* mutations.
In summary, **some prion diseases are hereditary due to mutations in the prion protein gene, while others occur sporadically or are acquired through infection.** The hereditary forms are caused by autosomal dominant mutations in *PRNP* and include fatal familial insomnia, Gerstmann-Sträussler-Scheinker disease, and familial Creutzfeldt-Jakob disease[1][2][3][4][5].
—
**Sources:**
[1] Fatal insomnia – Wikipedia
[2] Gerstmann-Sträussler-Scheinker Disease – NORD (National Organization for Rare Disorders)
[3] SSA – POMS: DI 23022.145 – Creutzfeldt-Jakob Disease (CJD) – Adult
[4] Major prion protein – Wikipedia
[5] Prion | Definition, Biology, & Disease – Britannica
