J Korean Med Sci.  2014 May;29(5):623-632. 10.3346/jkms.2014.29.5.623.

Genetic Studies in Human Prion Diseases

• Jeong BH
• Kim YS

• KMID: 1786101
• DOI: http://doi.org/10.3346/jkms.2014.29.5.623

Abstract

Human prion diseases are fatal neurodegenerative disorders that are characterized by spongiform changes, astrogliosis, and the accumulation of an abnormal prion protein (PrP(Sc)). Approximately 10%-15% of human prion diseases are familial variants that are caused by pathogenic mutations in the prion protein gene (PRNP). Point mutations or the insertions of one or more copies of a 24 bp repeat are associated with familial human prion diseases including familial Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler-Scheinker syndrome, and fatal familial insomnia. These mutations vary significantly in frequency between countries. Here, we compare the frequency of PRNP mutations between European countries and East Asians. Associations between single nucleotide polymorphisms (SNPs) of several candidate genes including PRNP and CJD have been reported. The SNP of PRNP at codon 129 has been shown to be associated with sporadic, iatrogenic, and variant CJD. The SNPs of several genes other than PRNP have been showed contradictory results. Case-control studies and genome-wide association studies have also been performed to identify candidate genes correlated with variant and/or sporadic CJD. This review provides a general overview of the genetic mutations and polymorphisms that have been analyzed in association with human prion diseases to date.

Keyword

Creutzfeldt-Jakob Disease; Genome-Wide Association Study; Prion Diseases; Mutation; Prion Protein Gene; Polymorphism, Single Nucleotide

MeSH Terms

Europe
Far East
Humans
Mutation
Polymorphism, Single Nucleotide
Prion Diseases/epidemiology/*genetics
Prions/*genetics
Prions

Figure

• 

  Fig. 1 Mutations in that PRNP gene the cause genetic Creutzfeldt-Jakob disease (CJD) or FFI in humans. D178N* is associated with familial CJD or fatal familial insomnia (FFI), depending on the allele present at codon 129 (Met, M = FFI, Val, V = familial CJD). The single-letter designations for the amino acids are as follows: D = aspartic acid, E = glutamic acid, G = glycine, H = histidine, I = isoleucine, K = lysine, M = methionine, N = asparagine, P = proline, Q = glutamine, R = arginine, S = serine, T = threonine, and V = valine. OPRI and OPRD indicate octapeptide repeat insertion and octapeptide repeat deletion, respectively. CHO, Asn-linked glycosylation sites; GPI, glycosylphosphatidylinositol.

• 

  Fig. 2 Mutations in the PRNP gene that cause Gerstmann-Sträussler-Scheinker syndrome (GSS). The single-letter designations for the amino acids are as follows: A = alanine, D = aspartic acid, E = glutamic acid, F = phenylalanine, H = histidine, L = leucine, N = asparagine, P = proline, Q = glutamine, R = arginine, S = serine, T = threonine, V = valine, and Y = tyrosine. OPRI indicates the octapeptide repeat insertion. The stop indicates a stop codon. CHO, Asn-linked glycosylation sites; GPI, glycosylphosphatidylinositol.

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