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

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Databases, Genetic
  • Datasets as Topic
  • Female
  • Genes, Dominant / genetics
  • Genetic Association Studies*
  • Genetic Counseling
  • Heterozygote
  • Humans
  • Male
  • Mutation, Missense*
  • Parkinson Disease / etiology
  • Parkinson Disease / genetics*
  • alpha-Synuclein / genetics*

Substances

  • SNCA protein, human
  • alpha-Synuclein