Insufficient evidence for pathogenicity of SNCA His50Gln (H50Q) in Parkinson's disease.
Insufficient evidence for pathogenicity of SNCA His50Gln (H50Q) in Parkinson's disease.
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DOI：
10.1016/j.neurobiolaging.2017.12.012
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发表时间：
2018-04
影响因子：
4.2
通讯作者：
Wood NW
中科院分区：
文献类型：
--
作者：
Blauwendraat C;Kia DA;Pihlstrøm L;Gan-Or Z;Lesage S;Gibbs JR;Ding J;Alcalay RN;Hassin-Baer S;Pittman AM;Brooks J;Edsall C;Chung SJ;Goldwurm S;Toft M;Schulte C;International Parkinson's Disease Genomics Consortium (IPDGC), COURAGE-PD Consortium;Hernandez D;Singleton AB;Nalls MA;Brice A;Scholz SW;Wood NW
SNCA错义突变是常染色体显性帕金森病（PD）的罕见原因。迄今为止，SNCA中的六个错义突变已被提名为因果突变。在这里，我们评估了这六种突变在公共人群数据库和PD病例对照数据集中的频率，以确定其真正的致病性。我们发现，六个报告的SNCA突变之一，His 50 Gln，在大型人群数据库中一致确定，与对照组相比，在PD病例中没有明显的富集。这些结果表明，His 50 Gln可能不是致病性变异。该信息对于为His 50 Gln携带者提供咨询非常重要，并对His 50 Gln α-突触核蛋白功能研究的解释具有意义。
SNCA missense mutations are a rare cause of autosomal dominant Parkinson’s disease (PD). To date, six missense mutations in SNCA have been nominated as causal. Here, we assess the frequency of these six mutations in public population databases and PD case-control datasets in order to determine their true pathogenicity. We found that one of the six 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.
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影响因子：
8.6
作者：
Appel-Cresswell, Silke;Vilarino-Guell, Carles;Farrer, Matthew J.
通讯作者：
Farrer, Matthew J.
影响因子：
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通讯作者：
Farrer, Matthew James
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通讯作者：
Myers, Richard H.