Dataset Information

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

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 ?-synuclein functional investigations.

SUBMITTER: Blauwendraat C

PROVIDER: S-EPMC5823280 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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

Blauwendraat Cornelis C Kia Demis A DA Pihlstrøm Lasse L Gan-Or Ziv Z Lesage Suzanne S Gibbs J Raphael JR Ding Jinhui J Alcalay Roy N RN Hassin-Baer Sharon S Pittman Alan M AM Brooks Janet J Edsall Connor C Chung Sun Ju SJ Goldwurm Stefano S Toft Mathias M Schulte Claudia C Hernandez Dena D Singleton Andrew B AB Nalls Mike A MA Brice Alexis A Scholz Sonja W SW Wood Nicholas W NW

Neurobiology of aging 20171220

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 re ...[more]

PMID: 29398121

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Project description:Intraneuronal inclusions of alpha-synuclein (α-synuclein, α-syn) are commonly found in the brain of patients with Parkinson's disease (PD). The pathogenesis of the abundant α-syn protein in the blood has been extensively studied to understand its properties better. In recent years, peptidome analysis has received increasing attention. In this study, we identified and analyzed serum peptides from wild-type (WT) and the (Thy-1)-h[A30P] alpha-synuclein transgenic mice (SNCA-A30P mice) using liquid chromatography-tandem mass spectrometry (LC-MS/MS). One thousand eight hundred fifty-six peptides from 771 proteins were analyzed. Among them, 151 peptides from 107 proteins were significantly differentially expressed. The glycoprotein VI platelet pathway (GP6) was the pathway's most significant differentially expressed signaling pathway. Cleavage sites of the differentially expressed peptides may reflect protease distribution and activity. We selected the most significantly differentially expressed peptide, VGGDPI, and found that it contained cathepsin K (Ctsk) and trypsin-1 cleavage sites, suggesting that Ctsk and trypsin-1 may be key peptidases in PD. α-syn is a protein associated with the pathogenesis of PD. mutations in several genes, including SNCA, which encodes α-syn, are associated with the development of PD. Bioinformatics analysis of the physiological pathways related to SNCA genes and apoptosis genes found the five most markedly up-regulated proteins: formin homology 2 domain-containing 1 (FHOD1), insulin receptor substrate 1(IRS1), TRPM8 channel-associated factor 1 (TCAF1), glyceraldehyde 3-phosphate dehydrogenase (GAPDH), and interleukin-16 (IL-16). Therefore, the differentially expressed peptides in the five precursor protein domains may be potential bioactive peptides associated with α-syn and apoptosis. This study provides a validated peptidomics profile of SNCA-A30P mice and identifies potentially bioactive peptides linked to α-syn and apoptosis.

Dataset Information

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

Publications

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

Similar Datasets

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