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However, the significance of this missense variant remained unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>We sought to elucidate whether V15A could increase aggregation or change phospholipid affinity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A sequencing analysis for the <jats:italic>SNCA<\/jats:italic> encoding \u03b1\u2010Syn from 875 patients with PD and 324 control subjects was performed. Comparing with known pathogenic missense variants of \u03b1\u2010Syn, A30P, and A53T, we analyzed the effects of V15A on binding to phospholipid membrane, self\u2010aggregation, and seed\u2010dependent aggregation in cultured cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Genetic screening identified <jats:italic>SNCA<\/jats:italic> c.44\u2009T&gt;C (p.V15A) from two Japanese PD families. The missense variant V15A was extremely rare in several public databases and predicted as pathogenic using <jats:italic>in silico<\/jats:italic> tools. The amplification activity of \u03b1\u2010Syn V15A fibrils was stronger than that of wild\u2010type \u03b1\u2010Syn fibrils.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The discovery of the V15A variant from Japanese families reinforces the possibility that the V15A variant may be a causative variant for developing PD. V15A had a reduced affinity for phospholipids and increased propagation activity compared with wild\u2010type. \u00a9 2022 The Authors. <jats:italic>Movement Disorders<\/jats:italic> published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.29162","type":"journal-article","created":{"date-parts":[[2022,7,27]],"date-time":"2022-07-27T08:24:37Z","timestamp":1658910277000},"page":"2075-2085","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["<scp>\u03b1\u2010Synuclein V15A<\/scp> Variant in Familial Parkinson's Disease Exhibits a Weaker Lipid\u2010Binding Property"],"prefix":"10.1002","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9177-9587","authenticated-orcid":false,"given":"Kensuke","family":"Daida","sequence":"first","affiliation":[{"name":"Department of Neurology Juntendo University School of Medicine  Tokyo 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