Neurodegenerative Diseases Research Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Department of Molecular Neurosciences, Institute of Neurology, University College London, London, UK.
Neurobiol Aging. 2018 Apr;64:159.e5-159.e8. doi: 10.1016/j.neurobiolaging.2017.12.012. Epub 2017 Dec 20.
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.
SNCA 错义突变是常染色体显性帕金森病 (PD) 的罕见病因。迄今为止，SNCA 中的 6 个错义突变被认为是致病原因。在此，我们评估了这 6 个突变在公共人群数据库和 PD 病例对照数据集的频率，以确定它们的真正致病性。我们发现，在大型人群数据库中，6 个报告的 SNCA 突变之一 His50Gln 始终被识别到，与对照组相比，PD 病例中没有明显富集。这些结果表明 His50Gln 可能不是一种致病性变异。此信息对于为 His50Gln 携带者提供咨询很重要，并且对 His50Gln α-突触核蛋白功能研究的解释具有影响。
