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Neurobiol Aging. 2018 Apr;64:159.e5-159.e8. doi: 10.1016/j.neurobiolaging.2017.12.012. Epub 2017 Dec 20.

Insufficient evidence for pathogenicity of SNCA His50Gln (H50Q) in Parkinson's disease.

Author information

1
Neurodegenerative Diseases Research Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
2
Department of Molecular Neurosciences, Institute of Neurology, University College London, London, UK.
3
Department of Neurology, Oslo University Hospital, Oslo, Norway.
4
Department of Human Genetics, McGill University, Montréal, Quebec, Canada; Department of Neurology & Neurosurgery, Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada.
5
Inserm U1127, CNRS UMR7225, Sorbonne Universités, UPMC Univ Paris 06, UMR_S1127, Institut du Cerveau et de la Moelle épinière, Paris, France.
6
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
7
Department of Neurology, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY, USA; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY, USA.
8
Department of Neurology and Sagol Neuroscience Center, Chaim Sheba Medical Center, The Movement Disorders Institute, Tel-Hashomer, Ramat Gan, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
9
Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
10
Parkinson Institute of Milan, ASST "Gaetano Pini/CTO", Milano, Italy; Department of Neuroscience, "Rita Levi Montalcini", University of Turin, Italy.
11
Department of Neurology, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
12
Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Germany.
13
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA; Founder/Consultant with Data Tecnica International, Glen Echo, MD, USA.
14
Neurodegenerative Diseases Research Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA; Department of Neurology, Johns Hopkins University Medical Center, Baltimore, MD, USA.
15
Department of Molecular Neurosciences, Institute of Neurology, University College London, London, UK. Electronic address: n.wood@ucl.ac.uk.

Abstract

SNCA missense mutations are a rare cause of autosomal dominant Parkinson's disease (PD). To date, 6 missense mutations in SNCA have been nominated as causal. Here, we assess the frequency of these 6 mutations in public population databases and PD case-control data sets to determine their true pathogenicity. We found that 1 of the 6 reported SNCA mutations, His50Gln, was consistently identified in large population databases, and no enrichment was evident in PD cases compared to controls. These results suggest that His50Gln is probably not a pathogenic variant. This information is important to provide counseling for His50Gln carriers and has implications for the interpretation of His50Gln α-synuclein functional investigations.

KEYWORDS:

H50Q; His50Gln; Parkinson's disease; SNCA

[Indexed for MEDLINE]
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