{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T20:29:48Z","timestamp":1791318588661,"version":"4.3.1"},"reference-count":34,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2013,5,21]],"date-time":"2013-05-21T00:00:00Z","timestamp":1369094400000},"content-version":"vor","delay-in-days":50,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2013,4]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      To date, 3 rare missense mutations in the\n                      <jats:italic>SNCA<\/jats:italic>\n                      (\u03b1\u2010synuclein) gene and the more frequent duplications or triplications of the wild\u2010type gene are known to cause a broad array of clinical and pathological symptoms in familial Parkinson disease (PD). Here, we describe a French family with a parkinsonian\u2013pyramidal syndrome harboring a novel heterozygous\n                      <jats:italic>SNCA<\/jats:italic>\n                      mutation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Whole exome sequencing of DNA from 3 patients in a 3\u2010generation pedigree was used to identify a new PD\u2010associated mutation in\n                      <jats:italic>SNCA<\/jats:italic>\n                      . Clinical and pathological features of the patients were analyzed. The cytotoxic effects of the mutant and wild\u2010type proteins were assessed by analytical ultracentrifugation, thioflavin T binding, transmission electron microscopy, cell viability assay, and caspase\u20103 activation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified a novel\n                      <jats:italic>SNCA<\/jats:italic>\n                      G51D (c.152 G&gt;A) mutation that cosegregated with the disease and was absent from controls. G51D was associated with an unusual PD phenotype characterized by early disease onset, moderate response to levodopa, rapid progression leading to loss of autonomy and death within a few years, marked pyramidal signs including bilateral extensor plantar reflexes, occasionally spasticity, and frequently psychiatric symptoms. Pathological lesions predominated in the basal ganglia and the pyramidal tracts and included fine, diffuse cytoplasmic inclusions containing phospho\u2010\u03b1\u2010synuclein in superficial layers of the cerebral cortex, including the entorhinal cortex. Functional studies showed that G51D \u03b1\u2010synuclein oligomerizes more slowly and its fibrils are more toxic than those of the wild\u2010type protein.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>\n                      We have identified a novel\n                      <jats:italic>SNCA<\/jats:italic>\n                      G51D mutation that causes a form of PD with unusual clinical, neuropathological, and biochemical features. Ann Neurol 2013;73:459\u2013471\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.23894","type":"journal-article","created":{"date-parts":[[2013,3,23]],"date-time":"2013-03-23T16:52:24Z","timestamp":1364057544000},"page":"459-471","source":"Crossref","is-referenced-by-count":697,"title":["G51D \u03b1\u2010synuclein mutation causes a novel Parkinsonian\u2013pyramidal syndrome"],"prefix":"10.1002","volume":"73","author":[{"given":"Suzanne","family":"Lesage","sequence":"first","affiliation":[{"name":"Pierre and Marie Curie University\u2013Paris 6 Research Center of the Institute for Brain and Spinal Cord, National Institute of Health and Medical Research Paris"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathieu","family":"Anheim","sequence":"additional","affiliation":[{"name":"Pierre and Marie Curie University\u2013Paris 6 Research Center of the Institute for Brain and Spinal Cord, National Institute of Health and Medical Research Paris"},{"name":"Department of Genetics and Cytogenetics"},{"name":"Reference Center for Neurogenetic Diseases of the Child and Adult Piti\u00e9\u2010Salp\u00eatri\u00e8re Hospital Paris"},{"name":"Neurology Service, Hautepierre Hospital University Hospitals of Strasbourg Strasbourg"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franck","family":"Letournel","sequence":"additional","affiliation":[{"name":"UF Neurobiology\u2013Neuropathology Institute of Biology in Health Angers"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc","family":"Bousset","sequence":"additional","affiliation":[{"name":"Laboratory of Enzymology and Structural Biochemistry National Center for Scientific Research Gif\u2010sur\u2010Yvette"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aur\u00e9lie","family":"Honor\u00e9","sequence":"additional","affiliation":[{"name":"Pierre and Marie Curie University\u2013Paris 6 Research Center of the Institute for Brain and Spinal Cord, National Institute of Health and Medical Research Paris"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nelly","family":"Rozas","sequence":"additional","affiliation":[{"name":"Pierre and Marie Curie University\u2013Paris 6 Research Center of the Institute for Brain and Spinal Cord, National Institute of Health and Medical Research Paris"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Pieri","sequence":"additional","affiliation":[{"name":"Laboratory of Enzymology and Structural Biochemistry National Center for Scientific Research Gif\u2010sur\u2010Yvette"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karine","family":"Madiona","sequence":"additional","affiliation":[{"name":"Laboratory of Enzymology and Structural Biochemistry National Center for Scientific Research Gif\u2010sur\u2010Yvette"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"D\u00fcrr","sequence":"additional","affiliation":[{"name":"Pierre and Marie Curie University\u2013Paris 6 Research Center of the Institute for Brain and Spinal Cord, National Institute of Health and Medical Research Paris"},{"name":"Department of Genetics and Cytogenetics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald","family":"Melki","sequence":"additional","affiliation":[{"name":"Laboratory of Enzymology and Structural Biochemistry National Center for Scientific Research Gif\u2010sur\u2010Yvette"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Verny","sequence":"additional","affiliation":[{"name":"University of Angers, National Center for Scientific Research, National Institute of Health and Medical Research and Neurology Service, National Reference Center for Neurogenetic Diseases, Angers University Hospital Center Angers France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis","family":"Brice","sequence":"additional","affiliation":[{"name":"Pierre and Marie Curie University\u2013Paris 6 Research Center of the Institute for Brain and Spinal Cord, National Institute of Health and Medical Research Paris"},{"name":"Department of Genetics and Cytogenetics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the French Parkinson's Disease Genetics Study 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