ArticleParkinsonism & related disorders2021
A new alpha-synuclein missense variant (Thr72Met) in two Turkish families with Parkinson's disease.
Article in Parkinsonism & related disorders, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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26 citing papers in PubMed, 40 citations in OpenAlex.
- Genetics of α-Synuclein: The Prime Pathological Player of Parkinson's Disease.Neurotoxicity research · 2026Review
- Synaptic vesicle architecture modulates α-synuclein conformation and pathogenic transitions in Parkinson's disease.Bioscience reports · 2026Review
- Gut microbiota and Parkinson's disease: exploring pathogenesis and potential therapeutic strategies from a gut-brain axis perspective.iScience · 2026Review
- A Novel α-Synuclein K58N Missense Variant in a Patient with Parkinson's Disease.Movement disorders : official journal of the Movement Disorder Society · 2025Article
- Neuropathology of Lewy body dementia: Lewy-related pathology, α-synuclein oligomers, and comorbid pathologies.Molecular neurodegeneration · 2025Review
- A novel alpha-synuclein G14R missense variant is associated with atypical neuropathological features.Molecular neurodegeneration · 2025Article
- Amyloid formation of alternatively spliced variants of α-synuclein.Protein science : a publication of the Protein Society · 2025Article
- Limitations and Applications of Rodent Models in Tauopathy and Synucleinopathy Research.Journal of neurochemistry · 2025Review
- A novel alpha-synuclein K58N missense variant in a patient with Parkinson's disease.medRxiv : the preprint server for health sciences · 2025Article
- The novel p.A30G SNCA pathogenic variant in Greek patients with familial and sporadic Parkinson's disease.European journal of neurology · 2025Article
- Exploring the Potential of Biomimetic Peptides in Targeting Fibrillar and Filamentous Alpha-Synuclein-An In Silico and Experimental Approach to Parkinson's Disease.Biomimetics (Basel, Switzerland) · 2024Article
- Structurally targeted mutagenesis identifies key residues supporting α-synuclein misfolding in multiple system atrophy.Journal of Parkinson's disease · 2024Article
- Research Priorities on the Role of α-Synuclein in Parkinson's Disease Pathogenesis.Movement disorders : official journal of the Movement Disorder Society · 2024Review
- Review
- Residues 2 to 7 of α-synuclein regulate amyloid formation via lipid-dependent and lipid-independent pathways.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Structurally targeted mutagenesis identifies key residues supportingbioRxiv : the preprint server for biology · 2024Article
- Article
- Resequencing the complete SNCA locus in Indian patients with Parkinson's disease.NPJ Parkinson's disease · 2024Article
- Ultrastructures of α-Synuclein Filaments in Synucleinopathy Brains and Experimental Models.Journal of movement disorders · 2024Article
- Updated benchmarking of variant effect predictors using deep mutational scanning.Molecular systems biology · 2023Article
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Authors and funding
15 authors at 5 institutions in 4 countries.
Funding
Abstract
introductionMissense variants and multiplications of the alpha-synuclein gene (SNCA) are established as rare causes of autosomal dominant forms of Parkinson's Disease (PD).
methodsTwo families of Turkish origins with PD were studied; the SNCA coding region was analyzed by Sanger sequencing, and by whole exome sequencing (WES) in the index patient of the first and the second family, respectively. Co-segregation studies and haplotype analysis across the SNCA locus were carried out. Functional studies included in vitro thioflavin-T aggregation assay and in silico structural modelling of the alpha-synuclein (α-syn) protein.
resultsWe identified a novel heterozygous SNCA variant, c.215C > T (p.Thr72Met), segregating with PD in a total of four members in the two families. A shared haplotype across the SNCA locus was found among variant carriers, suggestive of a common ancestor. We next showed that the Thr72Met α-syn displays enhanced aggregation in-vitro, compared to the wild-type species. In silico analysis of a tetrameric α-syn structural model revealed that Threonine 72 lies in the tetrameric interface, and substitution with the much larger methionine residue could potentially destabilize the tetramer.
conclusionWe present clinical, genetic, and functional data supporting a causative role of the SNCA c.215C > T (p.Thr72Met) variant in familial PD. Testing for this variant in patients with PD, especially of Turkish origin, might detect additional carriers. Further functional analyses might offer new insights into the shared biochemical properties of the PD-causing SNCA missense variants, and how they lead to neurodegeneration.
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