title: Analysis of the prion protein gene in multiple system atrophy.
abstract: 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.
authors: 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: v.chelban@ucl.ac.uk.
authors: Viorica
authors: V
authors: Chelban
authors: Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK; National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.
authors: Andreea
authors: A
authors: Manole
authors: 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.
authors: Lasse
authors: L
authors: Pihlstrøm
authors: Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK; National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.
authors: Lucia
authors: L
authors: Schottlaender
authors: Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK; National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.
authors: Stephanie
authors: S
authors: Efthymiou
authors: Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK; National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.
authors: Emer
authors: E
authors: OConnor
authors: 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.
authors: Wassilios G
authors: WG
authors: Meissner
authors: 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.
authors: Janice L
authors: JL
authors: Holton
authors: Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK; National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.
authors: Henry
authors: H
authors: Houlden
mesh_terms: D001921:Brain / Q000000981:diagnostic imaging; D003062:Codon / Q000235:genetics; D004843:Epistasis, Genetic; D059472:Exome / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D006720:Homozygote; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D019578:Multiple System Atrophy / Q000000981:diagnostic imaging / Q000235:genetics*; D011110:Polymorphism, Genetic; D000072002:Prion Proteins / Q000235:genetics*; D012307:Risk Factors; D017422:Sequence Analysis, DNA / Q000379:methods; D051844:alpha-Synuclein / Q000235:genetics
chemical_list: D003062:Codon; C512656:PRNP protein, human; D000072002:Prion Proteins; D051844:alpha-Synuclein
keywords: Multiple system atrophy; PRNP; Prion disease; Prion protein; Sporadic Creutzfeld-Jakob disease