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Acta Neuropathologica
Published in: Acta Neuropathologica 2/2015

01-08-2015 | Review

The influence of PRNP polymorphisms on human prion disease susceptibility: an update

Authors: Atsushi Kobayashi, Kenta Teruya, Yuichi Matsuura, Tsuyoshi Shirai, Yoshikazu Nakamura, Masahito Yamada, Hidehiro Mizusawa, Shirou Mohri, Tetsuyuki Kitamoto

Published in: Acta Neuropathologica | Issue 2/2015

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Abstract

Two normally occurring polymorphisms of the human PRNP gene, methionine (M)/valine (V) at codon 129 and glutamic acid (E)/lysine (K) at codon 219, can affect the susceptibility to prion diseases. It has long been recognized that 129M/M homozygotes are overrepresented in sporadic Creutzfeldt–Jakob disease (CJD) patients and variant CJD patients, whereas 219E/K heterozygotes are absent in sporadic CJD patients. In addition to these pioneering findings, recent progress in experimental transmission studies and worldwide surveillance of prion diseases have identified novel relationships between the PRNP polymorphisms and the prion disease susceptibility. For example, although 219E/K heterozygosity confers resistance against the development of sporadic CJD, this genotype is not entirely protective against acquired forms (iatrogenic CJD and variant CJD) or genetic forms (genetic CJD and Gerstmann–Sträussler–Scheinker syndrome) of prion diseases. In addition, 129M/V heterozygotes predispose to genetic CJD caused by a pathogenic PRNP mutation at codon 180. These findings show that the effects of the PRNP polymorphisms may be more complicated than previously thought. This review aims to summarize recent advances in our knowledge about the influence of the PRNP polymorphisms on the prion disease susceptibility.
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Metadata
Title
The influence of PRNP polymorphisms on human prion disease susceptibility: an update
Authors
Atsushi Kobayashi
Kenta Teruya
Yuichi Matsuura
Tsuyoshi Shirai
Yoshikazu Nakamura
Masahito Yamada
Hidehiro Mizusawa
Shirou Mohri
Tetsuyuki Kitamoto
Publication date
01-08-2015
Publisher
Springer Berlin Heidelberg
Published in
Acta Neuropathologica / Issue 2/2015
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI
https://doi.org/10.1007/s00401-015-1447-7

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