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

被引：23

作者：

Blauwendraat, Cornelis ^{[1
]}

Kia, Demis A. ^{[2
]}

Pihlstrom, Lasse ^{[3
]}

Gan-Or, Ziv ^{[4
,5
]}

Lesage, Suzanne ^{[6
]}

Gibbs, J. Raphael ^{[7
]}

Ding, Jinhui ^{[7
]}

Alcalay, Roy N. ^{[8
,9
]}

Hassin-Baer, Sharon ^{[10
,11
,12
]}

Pittman, Alan M. ^{[2
]}

Brooks, Janet ^{[7
]}

Edsall, Connor ^{[7
]}

Chung, Sun Ju ^{[13
]}

Goldwurm, Stefano ^{[14
,15
]}

Toft, Mathias ^{[4
,16
]}

Schulte, Claudia ^{[17
]}

Hernandez, Dena ^{[7
]}

Singleton, Andrew B. ^{[7
]}

Nalls, Mike A. ^{[7
,18
]}

Brice, Alexis ^{[6
]}

Scholz, Sonja W. ^{[19
]}

Wood, Nicholas W. ^{[2
]}

机构：

[1] NINDS, Neurodegenerat Dis Res Unit, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA

[2] UCL, Inst Neurol, Dept Mol Neurosci, London, England

[3] Oslo Univ Hosp, Dept Neurol, Oslo, Norway

[4] McGill Univ, Dept Human Genet, Montreal, PQ, Canada

[5] McGill Univ, Dept Neurol & Neurosurg, Montreal Neurol Inst, Montreal, PQ, Canada

[6] UPMC Univ Paris 06, Sorbonne Univ, Inst Cerveau & Moelle Epiniere, Inserm U1127,CNRS UMR7225,UMR S1127, Paris, France

[7] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA

[8] Columbia Univ Coll Phys & Surg, Dept Neurol, Med Ctr, New York, NY 10032 USA

[9] Columbia Univ Coll Phys & Surg, Taub Inst Res Alzheimers Dis & Aging Brain, 630 W 168th St, New York, NY 10032 USA

[10] Chaim Sheba Med Ctr, Dept Neurol, Movement Disorders Inst, Ramat Gan, Israel

[11] Chaim Sheba Med Ctr, Sagol Neurosci Ctr, Movement Disorders Inst, Ramat Gan, Israel

[12] Tel Aviv Univ, Sackler Fac Med, Tel Aviv, Israel

[13] Univ Ulsan, Dept Neurol, Asan Med Ctr, Coll Med, Seoul, South Korea

[14] ASST Gaetano Pini CTO, Parkinson Inst Milan, Milan, Italy

[15] Rita Levi Montalcini Univ Turin, Dept Neurosci, Turin, Italy

[16] Univ Oslo, Inst Clin Med, Oslo, Norway

[17] Univ Tubingen, Dept Neurodegenerat Dis, Hertie Inst Clin Brain Res, Tubingen, Germany

[18] Data Tecn Int, Glen Echo, MD USA

[19] Johns Hopkins Univ, Dept Neurol, Med Ctr, Baltimore, MD 21218 USA

来源：

NEUROBIOLOGY OF AGING | 2018年 / 64卷

基金：

美国国家卫生研究院;

关键词：

Parkinson's disease; SNCA; H50Q; His50Gln; ALPHA-SYNUCLEIN; SEQUENCE VARIANTS; MUTATION; PENETRANCE; GUIDELINES; GENOTYPE;

D O I：

10.1016/j.neurobiolaging.2017.12.012

中图分类号：

R592 [老年病学]; C [社会科学总论];

学科分类号：

03 ; 0303 ; 100203 ;

摘要：

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 a-synuclein functional investigations. Published by Elsevier Inc.

引用

页码：159.e5 / 159.e8

页数：4

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