Insufficient evidence for pathogenicity of SNCA His50Gln (H50Q) in Parkinson's disease
Cornelis Blauwendraat
(1)
,
Demis Kia
(2)
,
Lasse Pihlstrøm
(3)
,
Ziv Gan-Or
(4)
,
Suzanne Lesage
(5)
,
J Raphael Gibbs
(6)
,
Jinhui Ding
(6)
,
Roy Alcalay
(7)
,
Sharon Hassin-Baer
(8, 9)
,
Alan Pittman
(2)
,
Janet Brooks
(6)
,
Connor Edsall
(6)
,
Sun Ju Chung
(10)
,
Stefano Goldwurm
(11, 12)
,
Mathias Toft
(3, 13)
,
Claudia Schulte
(14)
,
Dena Hernandez
(6)
,
Andrew Singleton
(6)
,
Mike Nalls
(6)
,
Alexis Brice
(5)
,
Sonja Scholz
(1, 15)
,
Nicholas Wood
(2)
1
NINDS -
National Institute of Neurological Disorders and Stroke [Bethesda]
2 UCL Institute of Neurology, Queen Square [London]
3 Oslo University Hospital [Oslo]
4 McGill University = Université McGill [Montréal, Canada]
5 ICM - Institut du Cerveau = Paris Brain Institute
6 NIA - National Institute on Aging [Bethesda, USA]
7 CUMC - Columbia University Medical Center
8 Chaim Sheba Medical Center
9 Sackler Faculty of Medicine
10 Asan Medical Center [Seoul]
11 Centro Parkinson/Parkinson Institute, ASST ‘‘Gaetano Pini/CTO,’
12 UNITO - Università degli studi di Torino = University of Turin
13 Institute of Clinical Medicine [Oslo]
14 Hertie Institute for Clinical Brain Research [Tubingen]
15 Johns Hopkins University School of Medicine [Baltimore]
2 UCL Institute of Neurology, Queen Square [London]
3 Oslo University Hospital [Oslo]
4 McGill University = Université McGill [Montréal, Canada]
5 ICM - Institut du Cerveau = Paris Brain Institute
6 NIA - National Institute on Aging [Bethesda, USA]
7 CUMC - Columbia University Medical Center
8 Chaim Sheba Medical Center
9 Sackler Faculty of Medicine
10 Asan Medical Center [Seoul]
11 Centro Parkinson/Parkinson Institute, ASST ‘‘Gaetano Pini/CTO,’
12 UNITO - Università degli studi di Torino = University of Turin
13 Institute of Clinical Medicine [Oslo]
14 Hertie Institute for Clinical Brain Research [Tubingen]
15 Johns Hopkins University School of Medicine [Baltimore]
Mathias Toft
- Fonction : Auteur
Alexis Brice
- Fonction : Auteur
- PersonId : 1104774
- ORCID : 0000-0002-0941-3990
- IdRef : 050512935
Résumé
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.