Analysis of the prion protein gene in multiple system atrophy
Neurobiology of Aging. 2017-01-01; 49: 216.e15-216.e18
DOI: 10.1016/j.neurobiolaging.2016.09.021
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1. Neurobiol Aging. 2017 Jan;49:216.e15-216.e18. doi:
10.1016/j.neurobiolaging.2016.09.021. Epub 2016 Oct 3.
Analysis of the prion protein gene in multiple system atrophy.
Chelban V(1), Manole A(2), Pihlstrøm L(3), Schottlaender L(2), Efthymiou S(2),
OConnor E(2), Meissner WG(4), Holton JL(5), Houlden H(2).
Author information:
(1)Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK;
National Hospital for Neurology and Neurosurgery, Queen Square, London, UK;
Department of Neurology, Medical and Pharmaceutical State University N.
Testemitanu, Chisinau, Moldova. Electronic address: .
(2)Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK;
National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.
(3)Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK;
National Hospital for Neurology and Neurosurgery, Queen Square, London, UK;
Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
(4)Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293,
Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293,
Bordeaux, France; Centre de référence atrophie multisystématisée, CHU de
Bordeaux, Bordeaux, France.
(5)Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK;
National Hospital for Neurology and Neurosurgery, Queen Square, London, UK; Reta
Lila Weston Institute of Neurological Studies and Queen Square Brain Bank for
Neurological Disorders, London, UK.
Neurodegenerative diseases are a very diverse group of disorders but they share
some common mechanisms such as abnormally misfolded proteins with prion-like
propagation and aggregation. Creutzfeldt-Jakob disease (CJD) is the most
prevalent prion disease in humans. In the sporadic form of CJD the only known
risk factor is the codon 129 polymorphism. Recent reports suggested that
α-synuclein in multiple system atrophy (MSA) has similar pathogenic mechanisms as
the prion protein. Here we present 1 Italian family with MSA and prion disease.
Also, cases of concurrent MSA and prion pathology in the same individual or
family suggest the possibility of molecular interaction between prion protein and
α-synuclein in the process of protein accumulation and neurodegeneration,
warranting further investigations. We assessed the PRNP gene by whole-exome
sequencing in 264 pathologically confirmed MSA cases and 462 healthy controls to
determine whether the 2 diseases share similar risk factors. We then analyzed
codon 129 polymorphism by Sanger sequencing and compared with previously
published results in sporadic CJD. Homozygosity at codon 129 was present in 50%
of pathologically confirmed MSA cases and in 58% of normal controls (odds ratio,
0.7 (95% confidence interval of 0.5-0.9)) compared with 88.2% in sporadic CJD.
Our data show that the homozygous state of position 129 in the PRNP is not a risk
factor for MSA. No other variants in the PRNP gene were associated with increased
risk for MSA.
Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
DOI: 10.1016/j.neurobiolaging.2016.09.021
PMCID: PMC5156473
PMID: 27793473 [Indexed for MEDLINE]