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

Cornelis Blauwendraat, Demis A. Kia, Lasse Pihlstrøm, Ziv Gan-Or, Suzanne Lesage, J. Raphael Gibbs, Jinhui Ding, Roy N. Alcalay, Sharon Hassin-Baer, Alan M. Pittman, Janet Brooks, Connor Edsall, Sun Ju Chung, Stefano Goldwurm, Mathias Toft, Claudia Schulte, Dena Hernandez, Andrew B. Singleton, Mike A. Nalls, Alexis BriceSonja W. Scholz, Nicholas W. Wood*, Alastair J. Noyce, Arianna Tucci, Gavin Charlesworth, Manuela Tan, Henry Houlden, Huw R. Morris, Helene Plun-Favreau, Peter Holmans, John Hardy, Jose M. Bras, John Quinn, Kin Y. Mok, Kimberley Billingsley, Patrick Lewis, Rita Guerreiro, Ruth Lovering, Raquel Duran Ogalla, Lea R’bibo, Mina Ryten, Valentina Escott-Price, Viorica Chelban, Thomas Foltynie, Una Marie Sheerin, Nigel Williams, Fabrice Danjou, Jean Christophe Corvol, Maria Martinez, Rejko Krüger, International Parkinson's Disease Genomics Consortium (IPDGC), COURAGE-PD Consortium

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

22 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)159.e5-159.e8
JournalNeurobiology of Aging
Publication statusPublished - 1 Apr 2018
Externally publishedYes


  • H50Q
  • His50Gln
  • Parkinson's disease
  • SNCA


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