Early‐onset L‐dopa‐responsive parkinsonism with pyramidal signs due to ATP13A2, PLA2G6, FBXO7 and spatacsin mutations
Identifieur interne : 000100 ( Istex/Corpus ); précédent : 000099; suivant : 000101Early‐onset L‐dopa‐responsive parkinsonism with pyramidal signs due to ATP13A2, PLA2G6, FBXO7 and spatacsin mutations
Auteurs : Coro Paisán-Ruiz ; Rocio Guevara ; Monica Federoff ; Hasmet Hanagasi ; Fardaz Sina ; Elahe Elahi ; Susanne A. Schneider ; Petra Schwingenschuh ; Nin Bajaj ; Murat Emre ; Andrew B. Singleton ; John Hardy ; Kailash P. Bhatia ; Sebastian Brandner ; Andrew J. Lees ; Henry HouldenSource :
- Movement Disorders [ 0885-3185 ] ; 2010-09-15.
English descriptors
Abstract
Seven autosomal recessive genes associated with juvenile and young‐onset Levodopa‐responsive parkinsonism have been identified. Mutations in PRKN, DJ‐1, and PINK1 are associated with a rather pure parkinsonian phenotype, and have a more benign course with sustained treatment response and absence of dementia. On the other hand, Kufor‐Rakeb syndrome has additional signs, which distinguish it clearly from Parkinson's disease including supranuclear vertical gaze palsy, myoclonic jerks, pyramidal signs, and cognitive impairment. Neurodegeneration with brain iron accumulation type I (Hallervorden‐Spatz syndrome) due to mutations in PANK2 gene may share similar features with Kufor‐Rakeb syndrome. Mutations in three other genes, PLA2G6 (PARK14), FBXO7 (PARK15), and Spatacsin (SPG11) also produce clinical similar phenotypes in that they presented with rapidly progressive parkinsonism, initially responsive to Levodopa treatment but later, developed additional features including cognitive decline and loss of Levodopa responsiveness. Here, using homozygosity mapping and sequence analysis in families with complex parkinsonisms, we identified genetic defects in the ATP13A2 (1 family), PLA2G6 (1 family) FBXO7 (2 families), and SPG11 (1 family). The genetic heterogeneity was surprising given their initially common clinical features. On careful review, we found the FBXO7 cases to have a phenotype more similar to PRKN gene associated parkinsonism. The ATP13A2 and PLA2G6 cases were more seriously disabled with additional swallowing problems, dystonic features, severe in some, and usually pyramidal involvement including pyramidal weakness. These data suggest that these four genes account for many cases of Levodopa responsive parkinsonism with pyramidal signs cases formerly categorized clinically as pallido‐pyramidal syndrome. © 2010 Movement Disorder Society.
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DOI: 10.1002/mds.23221
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Schneider</name><affiliation><mods:affiliation>Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, Queen Square, London, United Kingdom</mods:affiliation></affiliation><affiliation><mods:affiliation>Schilling Section of Clinical and Molecular Neurogenetics, Department of Neurology, University Luebeck, Germany</mods:affiliation></affiliation></author><author><name sortKey="Schwingenschuh, Petra" sort="Schwingenschuh, Petra" uniqKey="Schwingenschuh P" first="Petra" last="Schwingenschuh">Petra Schwingenschuh</name><affiliation><mods:affiliation>Schilling Section of Clinical and Molecular Neurogenetics, Department of Neurology, University Luebeck, Germany</mods:affiliation></affiliation></author><author><name sortKey="Bajaj, Nin" sort="Bajaj, Nin" uniqKey="Bajaj N" first="Nin" last="Bajaj">Nin Bajaj</name><affiliation><mods:affiliation>Department of Neurology, Queens Medical Center, University of Nottingham, Nottingham, United Kingdom</mods:affiliation></affiliation></author><author><name sortKey="Emre, Murat" sort="Emre, Murat" uniqKey="Emre M" first="Murat" last="Emre">Murat Emre</name><affiliation><mods:affiliation>Department of Neurology, Behavioral Neurology and Movement Disorders Unit, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey</mods:affiliation></affiliation></author><author><name sortKey="Singleton, Andrew B" sort="Singleton, Andrew B" uniqKey="Singleton A" first="Andrew B." last="Singleton">Andrew B. Singleton</name><affiliation><mods:affiliation>Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Mary Land, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>Public Health Sciences and Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia, USA</mods:affiliation></affiliation></author><author><name sortKey="Hardy, John" sort="Hardy, John" uniqKey="Hardy J" first="John" last="Hardy">John Hardy</name><affiliation><mods:affiliation>Department of Molecular Neuroscience and Reta Lila Weston Institute, UCL Institute of Neurology, London, Queen Square, London, United Kingdom</mods:affiliation></affiliation></author><author><name sortKey="Bhatia, Kailash P" sort="Bhatia, Kailash P" uniqKey="Bhatia K" first="Kailash P." last="Bhatia">Kailash P. Bhatia</name><affiliation><mods:affiliation>Schilling Section of Clinical and Molecular Neurogenetics, Department of Neurology, University Luebeck, Germany</mods:affiliation></affiliation></author><author><name sortKey="Brandner, Sebastian" sort="Brandner, Sebastian" uniqKey="Brandner S" first="Sebastian" last="Brandner">Sebastian Brandner</name><affiliation><mods:affiliation>Division of Neuropathology, UCL Institute of Neurology, Queen Square, London WC1N 3BG, United Kingdom</mods:affiliation></affiliation></author><author><name sortKey="Lees, Andrew J" sort="Lees, Andrew J" uniqKey="Lees A" first="Andrew J." last="Lees">Andrew J. Lees</name><affiliation><mods:affiliation>Department of Molecular Neuroscience and Reta Lila Weston Institute, UCL Institute of Neurology, London, Queen Square, London, United Kingdom</mods:affiliation></affiliation></author><author><name sortKey="Houlden, Henry" sort="Houlden, Henry" uniqKey="Houlden H" first="Henry" last="Houlden">Henry Houlden</name><affiliation><mods:affiliation>Department of Molecular Neuroscience and Reta Lila Weston Institute, UCL Institute of Neurology, London, Queen Square, London, United Kingdom</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Movement Disorders</title><title level="j" type="abbrev">Mov. Disord.</title><idno type="ISSN">0885-3185</idno><idno type="eISSN">1531-8257</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2010-09-15">2010-09-15</date><biblScope unit="vol">25</biblScope><biblScope unit="issue">12</biblScope><biblScope unit="page" from="1791">1791</biblScope><biblScope unit="page" to="1800">1800</biblScope></imprint><idno type="ISSN">0885-3185</idno></series><idno type="istex">2E3B8506FEF133B82EECBF1E333493CB60F5080E</idno><idno type="DOI">10.1002/mds.23221</idno><idno type="ArticleID">MDS23221</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0885-3185</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>ATP13A2</term><term>FBXO7</term><term>PLA2G6</term><term>Spatacsin</term><term>parkinsonism</term><term>recessive</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Seven autosomal recessive genes associated with juvenile and young‐onset Levodopa‐responsive parkinsonism have been identified. Mutations in PRKN, DJ‐1, and PINK1 are associated with a rather pure parkinsonian phenotype, and have a more benign course with sustained treatment response and absence of dementia. On the other hand, Kufor‐Rakeb syndrome has additional signs, which distinguish it clearly from Parkinson's disease including supranuclear vertical gaze palsy, myoclonic jerks, pyramidal signs, and cognitive impairment. Neurodegeneration with brain iron accumulation type I (Hallervorden‐Spatz syndrome) due to mutations in PANK2 gene may share similar features with Kufor‐Rakeb syndrome. Mutations in three other genes, PLA2G6 (PARK14), FBXO7 (PARK15), and Spatacsin (SPG11) also produce clinical similar phenotypes in that they presented with rapidly progressive parkinsonism, initially responsive to Levodopa treatment but later, developed additional features including cognitive decline and loss of Levodopa responsiveness. Here, using homozygosity mapping and sequence analysis in families with complex parkinsonisms, we identified genetic defects in the ATP13A2 (1 family), PLA2G6 (1 family) FBXO7 (2 families), and SPG11 (1 family). The genetic heterogeneity was surprising given their initially common clinical features. On careful review, we found the FBXO7 cases to have a phenotype more similar to PRKN gene associated parkinsonism. The ATP13A2 and PLA2G6 cases were more seriously disabled with additional swallowing problems, dystonic features, severe in some, and usually pyramidal involvement including pyramidal weakness. These data suggest that these four genes account for many cases of Levodopa responsive parkinsonism with pyramidal signs cases formerly categorized clinically as pallido‐pyramidal syndrome. © 2010 Movement Disorder Society.</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Coro Paisán‐Ruiz PhD</name><affiliations><json:string>Department of Molecular Neuroscience and Reta Lila Weston Institute, UCL Institute of Neurology, London, Queen Square, London, United Kingdom</json:string></affiliations></json:item><json:item><name>Rocio Guevara BSc</name><affiliations><json:string>Department of Molecular Neuroscience and Reta Lila Weston Institute, UCL Institute of Neurology, London, Queen Square, London, United Kingdom</json:string></affiliations></json:item><json:item><name>Monica Federoff MS</name><affiliations><json:string>Department of Molecular Neuroscience and Reta Lila Weston Institute, UCL Institute of Neurology, London, Queen Square, London, United Kingdom</json:string></affiliations></json:item><json:item><name>Hasmet Hanagasi MD</name><affiliations><json:string>Department of Neurology, Behavioral Neurology and Movement Disorders Unit, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey</json:string></affiliations></json:item><json:item><name>Fardaz Sina MD</name><affiliations><json:string>Iran University of Medical Sciences, Hazrat Rasool Hospital, Tehran, Iran</json:string></affiliations></json:item><json:item><name>Elahe Elahi PhD</name><affiliations><json:string>Department of Biotechnology, University of Tehran, Tehran, Iran</json:string><json:string>School of Biology, University College of Science, University of Tehran, Tehran, Iran</json:string><json:string>Center of Excellence in Biomathematics, School of Mathematics, Statistics and Computer Science, College of Science, University of Tehran, Tehran, Iran</json:string></affiliations></json:item><json:item><name>Susanne A. Schneider MD</name><affiliations><json:string>Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, Queen Square, London, United Kingdom</json:string><json:string>Schilling Section of Clinical and Molecular Neurogenetics, Department of Neurology, University Luebeck, Germany</json:string></affiliations></json:item><json:item><name>Petra Schwingenschuh MD</name><affiliations><json:string>Schilling Section of Clinical and Molecular Neurogenetics, Department of Neurology, University Luebeck, Germany</json:string></affiliations></json:item><json:item><name>Nin Bajaj MD</name><affiliations><json:string>Department of Neurology, Queens Medical Center, University of Nottingham, Nottingham, United Kingdom</json:string></affiliations></json:item><json:item><name>Murat Emre MD</name><affiliations><json:string>Department of Neurology, Behavioral Neurology and Movement Disorders Unit, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey</json:string></affiliations></json:item><json:item><name>Andrew B. Singleton PhD</name><affiliations><json:string>Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Mary Land, USA</json:string><json:string>Public Health Sciences and Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia, USA</json:string></affiliations></json:item><json:item><name>John Hardy PhD</name><affiliations><json:string>Department of Molecular Neuroscience and Reta Lila Weston Institute, UCL Institute of Neurology, London, Queen Square, London, United Kingdom</json:string></affiliations></json:item><json:item><name>Kailash P. Bhatia MD</name><affiliations><json:string>Schilling Section of Clinical and Molecular Neurogenetics, Department of Neurology, University Luebeck, Germany</json:string></affiliations></json:item><json:item><name>Sebastian Brandner PhD</name><affiliations><json:string>Division of Neuropathology, UCL Institute of Neurology, Queen Square, London WC1N 3BG, United Kingdom</json:string></affiliations></json:item><json:item><name>Andrew J. Lees MD</name><affiliations><json:string>Department of Molecular Neuroscience and Reta Lila Weston Institute, UCL Institute of Neurology, London, Queen Square, London, United Kingdom</json:string></affiliations></json:item><json:item><name>Henry Houlden MD</name><affiliations><json:string>Department of Molecular Neuroscience and Reta Lila Weston Institute, UCL Institute of Neurology, London, Queen Square, London, United Kingdom</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>parkinsonism</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>recessive</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>ATP13A2</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>PLA2G6</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>FBXO7</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Spatacsin</value></json:item></subject><language><json:string>eng</json:string></language><abstract>Seven autosomal recessive genes associated with juvenile and young‐onset Levodopa‐responsive parkinsonism have been identified. Mutations in PRKN, DJ‐1, and PINK1 are associated with a rather pure parkinsonian phenotype, and have a more benign course with sustained treatment response and absence of dementia. On the other hand, Kufor‐Rakeb syndrome has additional signs, which distinguish it clearly from Parkinson's disease including supranuclear vertical gaze palsy, myoclonic jerks, pyramidal signs, and cognitive impairment. Neurodegeneration with brain iron accumulation type I (Hallervorden‐Spatz syndrome) due to mutations in PANK2 gene may share similar features with Kufor‐Rakeb syndrome. Mutations in three other genes, PLA2G6 (PARK14), FBXO7 (PARK15), and Spatacsin (SPG11) also produce clinical similar phenotypes in that they presented with rapidly progressive parkinsonism, initially responsive to Levodopa treatment but later, developed additional features including cognitive decline and loss of Levodopa responsiveness. Here, using homozygosity mapping and sequence analysis in families with complex parkinsonisms, we identified genetic defects in the ATP13A2 (1 family), PLA2G6 (1 family) FBXO7 (2 families), and SPG11 (1 family). The genetic heterogeneity was surprising given their initially common clinical features. On careful review, we found the FBXO7 cases to have a phenotype more similar to PRKN gene associated parkinsonism. The ATP13A2 and PLA2G6 cases were more seriously disabled with additional swallowing problems, dystonic features, severe in some, and usually pyramidal involvement including pyramidal weakness. These data suggest that these four genes account for many cases of Levodopa responsive parkinsonism with pyramidal signs cases formerly categorized clinically as pallido‐pyramidal syndrome. © 2010 Movement Disorder Society.</abstract><qualityIndicators><score>8</score><pdfVersion>1.3</pdfVersion><pdfPageSize>612 x 810 pts</pdfPageSize><refBibsNative>true</refBibsNative><abstractCharCount>1871</abstractCharCount><pdfWordCount>5001</pdfWordCount><pdfCharCount>34515</pdfCharCount><pdfPageCount>10</pdfPageCount><abstractWordCount>251</abstractWordCount></qualityIndicators><title>Early‐onset L‐dopa‐responsive parkinsonism with pyramidal signs due to ATP13A2, PLA2G6, FBXO7 and spatacsin mutations</title><genre><json:string>Serial article</json:string></genre><host><volume>25</volume><pages><total>10</total><last>1800</last><first>1791</first></pages><issn><json:string>0885-3185</json:string></issn><issue>12</issue><subject><json:item><value>Research Article</value></json:item></subject><genre></genre><language><json:string>unknown</json:string></language><title>Movement Disorders</title><doi><json:string>10.1002/(ISSN)1531-8257</json:string></doi></host><publicationDate>2010</publicationDate><copyrightDate>2010</copyrightDate><doi><json:string>10.1002/mds.23221</json:string></doi><id>2E3B8506FEF133B82EECBF1E333493CB60F5080E</id><fulltext><json:item><original>true</original><mimetype>application/pdf</mimetype><extension>pdf</extension><uri>https://api.istex.fr/document/2E3B8506FEF133B82EECBF1E333493CB60F5080E/fulltext/pdf</uri></json:item><json:item><original>false</original><mimetype>application/zip</mimetype><extension>zip</extension><uri>https://api.istex.fr/document/2E3B8506FEF133B82EECBF1E333493CB60F5080E/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/2E3B8506FEF133B82EECBF1E333493CB60F5080E/fulltext/tei"><teiHeader type="text"><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Early‐onset L‐dopa‐responsive parkinsonism with pyramidal signs due to ATP13A2, PLA2G6, FBXO7 and spatacsin mutations</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><availability><p>Wiley Subscription Services, Inc., A Wiley Company</p></availability><date>2010</date></publicationStmt><notesStmt><note type="content">*Potential conflict of interest: Nothing to report.</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Early‐onset L‐dopa‐responsive parkinsonism with pyramidal signs due to ATP13A2, PLA2G6, FBXO7 and spatacsin mutations</title><author><persName><forename type="first">Coro</forename><surname>Paisán‐Ruiz</surname><roleName type="degree">PhD</roleName></persName><affiliation>Department of Molecular Neuroscience and Reta Lila Weston Institute, UCL Institute of Neurology, London, Queen Square, London, United Kingdom</affiliation></author><author><persName><forename type="first">Rocio</forename><surname>Guevara</surname><roleName type="degree">BSc</roleName></persName><affiliation>Department of Molecular Neuroscience and Reta Lila Weston Institute, UCL Institute of Neurology, London, Queen Square, London, United Kingdom</affiliation></author><author><persName><forename type="first">Monica</forename><surname>Federoff</surname><roleName type="degree">MS</roleName></persName><affiliation>Department of Molecular Neuroscience and Reta Lila Weston Institute, UCL Institute of Neurology, London, Queen Square, London, United Kingdom</affiliation></author><author><persName><forename type="first">Hasmet</forename><surname>Hanagasi</surname><roleName type="degree">MD</roleName></persName><affiliation>Department of Neurology, Behavioral Neurology and Movement Disorders Unit, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey</affiliation></author><author><persName><forename type="first">Fardaz</forename><surname>Sina</surname><roleName type="degree">MD</roleName></persName><affiliation>Iran University of Medical Sciences, Hazrat Rasool Hospital, Tehran, Iran</affiliation></author><author><persName><forename type="first">Elahe</forename><surname>Elahi</surname><roleName type="degree">PhD</roleName></persName><affiliation>Department of Biotechnology, University of Tehran, Tehran, Iran</affiliation><affiliation>School of Biology, University College of Science, University of Tehran, Tehran, Iran</affiliation><affiliation>Center of Excellence in Biomathematics, School of Mathematics, Statistics and Computer Science, College of Science, University of Tehran, Tehran, Iran</affiliation></author><author><persName><forename type="first">Susanne A.</forename><surname>Schneider</surname><roleName type="degree">MD</roleName></persName><affiliation>Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, Queen Square, London, United Kingdom</affiliation><affiliation>Schilling Section of Clinical and Molecular Neurogenetics, Department of Neurology, University Luebeck, Germany</affiliation></author><author><persName><forename type="first">Petra</forename><surname>Schwingenschuh</surname><roleName type="degree">MD</roleName></persName><affiliation>Schilling Section of Clinical and Molecular Neurogenetics, Department of Neurology, University Luebeck, Germany</affiliation></author><author><persName><forename type="first">Nin</forename><surname>Bajaj</surname><roleName type="degree">MD</roleName></persName><affiliation>Department of Neurology, Queens Medical Center, University of Nottingham, Nottingham, United Kingdom</affiliation></author><author><persName><forename type="first">Murat</forename><surname>Emre</surname><roleName type="degree">MD</roleName></persName><affiliation>Department of Neurology, Behavioral Neurology and Movement Disorders Unit, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey</affiliation></author><author><persName><forename type="first">Andrew B.</forename><surname>Singleton</surname><roleName type="degree">PhD</roleName></persName><affiliation>Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Mary Land, USA</affiliation><affiliation>Public Health Sciences and Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia, USA</affiliation></author><author><persName><forename type="first">John</forename><surname>Hardy</surname><roleName type="degree">PhD</roleName></persName><affiliation>Department of Molecular Neuroscience and Reta Lila Weston Institute, UCL Institute of Neurology, London, Queen Square, London, United Kingdom</affiliation></author><author><persName><forename type="first">Kailash P.</forename><surname>Bhatia</surname><roleName type="degree">MD</roleName></persName><note type="correspondence"><p>Correspondence: Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, Queen Square, London, United Kingdom, WCIN 3BG</p></note><affiliation>Schilling Section of Clinical and Molecular Neurogenetics, Department of Neurology, University Luebeck, Germany</affiliation></author><author><persName><forename type="first">Sebastian</forename><surname>Brandner</surname><roleName type="degree">PhD</roleName></persName><affiliation>Division of Neuropathology, UCL Institute of Neurology, Queen Square, London WC1N 3BG, United Kingdom</affiliation></author><author><persName><forename type="first">Andrew J.</forename><surname>Lees</surname><roleName type="degree">MD</roleName></persName><affiliation>Department of Molecular Neuroscience and Reta Lila Weston Institute, UCL Institute of Neurology, London, Queen Square, London, United Kingdom</affiliation></author><author><persName><forename type="first">Henry</forename><surname>Houlden</surname><roleName type="degree">MD</roleName></persName><affiliation>Department of Molecular Neuroscience and Reta Lila Weston Institute, UCL Institute of Neurology, London, Queen Square, London, United Kingdom</affiliation></author></analytic><monogr><title level="j">Movement Disorders</title><title level="j" type="abbrev">Mov. Disord.</title><idno type="pISSN">0885-3185</idno><idno type="eISSN">1531-8257</idno><idno type="DOI">10.1002/(ISSN)1531-8257</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2010-09-15"></date><biblScope unit="vol">25</biblScope><biblScope unit="issue">12</biblScope><biblScope unit="page" from="1791">1791</biblScope><biblScope unit="page" to="1800">1800</biblScope></imprint></monogr><idno type="istex">2E3B8506FEF133B82EECBF1E333493CB60F5080E</idno><idno type="DOI">10.1002/mds.23221</idno><idno type="ArticleID">MDS23221</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2010</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Seven autosomal recessive genes associated with juvenile and young‐onset Levodopa‐responsive parkinsonism have been identified. Mutations in PRKN, DJ‐1, and PINK1 are associated with a rather pure parkinsonian phenotype, and have a more benign course with sustained treatment response and absence of dementia. On the other hand, Kufor‐Rakeb syndrome has additional signs, which distinguish it clearly from Parkinson's disease including supranuclear vertical gaze palsy, myoclonic jerks, pyramidal signs, and cognitive impairment. Neurodegeneration with brain iron accumulation type I (Hallervorden‐Spatz syndrome) due to mutations in PANK2 gene may share similar features with Kufor‐Rakeb syndrome. Mutations in three other genes, PLA2G6 (PARK14), FBXO7 (PARK15), and Spatacsin (SPG11) also produce clinical similar phenotypes in that they presented with rapidly progressive parkinsonism, initially responsive to Levodopa treatment but later, developed additional features including cognitive decline and loss of Levodopa responsiveness. Here, using homozygosity mapping and sequence analysis in families with complex parkinsonisms, we identified genetic defects in the ATP13A2 (1 family), PLA2G6 (1 family) FBXO7 (2 families), and SPG11 (1 family). The genetic heterogeneity was surprising given their initially common clinical features. On careful review, we found the FBXO7 cases to have a phenotype more similar to PRKN gene associated parkinsonism. The ATP13A2 and PLA2G6 cases were more seriously disabled with additional swallowing problems, dystonic features, severe in some, and usually pyramidal involvement including pyramidal weakness. These data suggest that these four genes account for many cases of Levodopa responsive parkinsonism with pyramidal signs cases formerly categorized clinically as pallido‐pyramidal syndrome. © 2010 Movement Disorder Society.</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Keywords</head><item><term>parkinsonism</term></item><item><term>recessive</term></item><item><term>ATP13A2</term></item><item><term>PLA2G6</term></item><item><term>FBXO7</term></item><item><term>Spatacsin</term></item></list></keywords></textClass><textClass><keywords scheme="Journal Subject"><list><head>Article category</head><item><term>Research Article</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2010-01-18">Received</change><change when="2010-04-07">Registration</change><change when="2010-09-15">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/2E3B8506FEF133B82EECBF1E333493CB60F5080E/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Wiley, elements deleted: body"><istex:xmlDeclaration>version="1.0" encoding="UTF-8" standalone="yes"</istex:xmlDeclaration><istex:document><component version="2.0" type="serialArticle" xml:lang="en"><header><publicationMeta level="product"><publisherInfo><publisherName>Wiley Subscription Services, Inc., A Wiley Company</publisherName><publisherLoc>Hoboken</publisherLoc></publisherInfo><doi registered="yes">10.1002/(ISSN)1531-8257</doi><issn type="print">0885-3185</issn><issn type="electronic">1531-8257</issn><idGroup><id type="product" value="MDS"></id></idGroup><titleGroup><title type="main" xml:lang="en" sort="MOVEMENT DISORDERS">Movement Disorders</title><title type="short">Mov. Disord.</title></titleGroup></publicationMeta><publicationMeta level="part" position="120"><doi origin="wiley" registered="yes">10.1002/mds.v25:12</doi><numberingGroup><numbering type="journalVolume" number="25">25</numbering><numbering type="journalIssue">12</numbering></numberingGroup><coverDate startDate="2010-09-15">15 September 2010</coverDate></publicationMeta><publicationMeta level="unit" type="article" position="40" status="forIssue"><doi origin="wiley" registered="yes">10.1002/mds.23221</doi><idGroup><id type="unit" value="MDS23221"></id></idGroup><countGroup><count type="pageTotal" number="10"></count></countGroup><titleGroup><title type="articleCategory">Research Article</title><title type="tocHeading1">Research Articles</title></titleGroup><copyright ownership="thirdParty">Copyright © 2010 Movement Disorder Society</copyright><eventGroup><event type="manuscriptReceived" date="2010-01-18"></event><event type="manuscriptRevised" date="2010-03-16"></event><event 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href="file:MDS.MDS23221.pdf"></link></linkGroup></publicationMeta><contentMeta><countGroup><count type="figureTotal" number="2"></count><count type="tableTotal" number="2"></count><count type="referenceTotal" number="39"></count><count type="wordTotal" number="6470"></count></countGroup><titleGroup><title type="main" xml:lang="en">Early‐onset L‐dopa‐responsive parkinsonism with pyramidal signs due to <i>ATP13A2, PLA2G6, FBXO7</i> and <i>spatacsin</i> mutations<link href="#fn2"></link></title><title type="short" xml:lang="en">Complex Recessive Parkinsonisms</title></titleGroup><creators><creator xml:id="au1" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Coro</givenNames><familyName>Paisán‐Ruiz</familyName><degrees>PhD</degrees></personName></creator><creator xml:id="au2" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Rocio</givenNames><familyName>Guevara</familyName><degrees>BSc</degrees></personName></creator><creator xml:id="au3" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Monica</givenNames><familyName>Federoff</familyName><degrees>MS</degrees></personName></creator><creator xml:id="au4" creatorRole="author" affiliationRef="#af2"><personName><givenNames>Hasmet</givenNames><familyName>Hanagasi</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au5" creatorRole="author" affiliationRef="#af3"><personName><givenNames>Fardaz</givenNames><familyName>Sina</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au6" creatorRole="author" affiliationRef="#af4 #af5 #af6"><personName><givenNames>Elahe</givenNames><familyName>Elahi</familyName><degrees>PhD</degrees></personName></creator><creator xml:id="au7" creatorRole="author" affiliationRef="#af7 #af8"><personName><givenNames>Susanne A.</givenNames><familyName>Schneider</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au8" creatorRole="author" affiliationRef="#af8"><personName><givenNames>Petra</givenNames><familyName>Schwingenschuh</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au9" creatorRole="author" affiliationRef="#af9"><personName><givenNames>Nin</givenNames><familyName>Bajaj</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au10" creatorRole="author" affiliationRef="#af2"><personName><givenNames>Murat</givenNames><familyName>Emre</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au11" creatorRole="author" affiliationRef="#af10 #af11"><personName><givenNames>Andrew B.</givenNames><familyName>Singleton</familyName><degrees>PhD</degrees></personName></creator><creator xml:id="au12" creatorRole="author" affiliationRef="#af1"><personName><givenNames>John</givenNames><familyName>Hardy</familyName><degrees>PhD</degrees></personName></creator><creator xml:id="au13" creatorRole="author" affiliationRef="#af8" corresponding="yes"><personName><givenNames>Kailash P.</givenNames><familyName>Bhatia</familyName><degrees>MD</degrees></personName><contactDetails><email>k.bhatia@ion.ucl.ac.uk</email></contactDetails></creator><creator xml:id="au14" creatorRole="author" affiliationRef="#af12"><personName><givenNames>Sebastian</givenNames><familyName>Brandner</familyName><degrees>PhD</degrees></personName></creator><creator xml:id="au15" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Andrew J.</givenNames><familyName>Lees</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au16" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Henry</givenNames><familyName>Houlden</familyName><degrees>MD</degrees></personName></creator></creators><affiliationGroup><affiliation xml:id="af1" countryCode="GB" type="organization"><unparsedAffiliation>Department of Molecular Neuroscience and Reta Lila Weston Institute, UCL Institute of Neurology, London, Queen Square, London, United Kingdom</unparsedAffiliation></affiliation><affiliation xml:id="af2" countryCode="TR" type="organization"><unparsedAffiliation>Department of Neurology, Behavioral Neurology and Movement Disorders Unit, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey</unparsedAffiliation></affiliation><affiliation xml:id="af3" countryCode="IR" type="organization"><unparsedAffiliation>Iran University of Medical Sciences, Hazrat Rasool Hospital, Tehran, Iran</unparsedAffiliation></affiliation><affiliation xml:id="af4" countryCode="IR" type="organization"><unparsedAffiliation>Department of Biotechnology, University of Tehran, Tehran, Iran</unparsedAffiliation></affiliation><affiliation xml:id="af5" countryCode="IR" type="organization"><unparsedAffiliation>School of Biology, University College of Science, University of Tehran, Tehran, Iran</unparsedAffiliation></affiliation><affiliation xml:id="af6" countryCode="IR" type="organization"><unparsedAffiliation>Center of Excellence in Biomathematics, School of Mathematics, Statistics and Computer Science, College of Science, University of Tehran, Tehran, Iran</unparsedAffiliation></affiliation><affiliation xml:id="af7" countryCode="GB" type="organization"><unparsedAffiliation>Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, Queen Square, London, United Kingdom</unparsedAffiliation></affiliation><affiliation xml:id="af8" countryCode="DE" type="organization"><unparsedAffiliation>Schilling Section of Clinical and Molecular Neurogenetics, Department of Neurology, University Luebeck, Germany</unparsedAffiliation></affiliation><affiliation xml:id="af9" countryCode="GB" type="organization"><unparsedAffiliation>Department of Neurology, Queens Medical Center, University of Nottingham, Nottingham, United Kingdom</unparsedAffiliation></affiliation><affiliation xml:id="af10" countryCode="US" type="organization"><unparsedAffiliation>Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Mary Land, USA</unparsedAffiliation></affiliation><affiliation xml:id="af11" countryCode="US" type="organization"><unparsedAffiliation>Public Health Sciences and Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia, USA</unparsedAffiliation></affiliation><affiliation xml:id="af12" countryCode="GB" type="organization"><unparsedAffiliation>Division of Neuropathology, UCL Institute of Neurology, Queen Square, London WC1N 3BG, United Kingdom</unparsedAffiliation></affiliation></affiliationGroup><keywordGroup xml:lang="en" type="author"><keyword xml:id="kwd1">parkinsonism</keyword><keyword xml:id="kwd2">recessive</keyword><keyword xml:id="kwd3">ATP13A2</keyword><keyword xml:id="kwd4">PLA2G6</keyword><keyword xml:id="kwd5">FBXO7</keyword><keyword xml:id="kwd6">Spatacsin</keyword></keywordGroup><supportingInformation><p> Additional Supporting Information may be found in the online version of this article. </p><supportingInfoItem><mediaResource alt="supporting information" href="urn-x:wiley:08853185:media:mds23221:MDS_23221_sm_suppinfo1"></mediaResource><caption>Supplementary_Material 1: Genomic sequences of the primes employed to amplify the coding and intron‐exon boundaries of the ATP13A2, PLA2G6, FBXO7 and Spatacsin genes.</caption></supportingInfoItem><supportingInfoItem><mediaResource alt="supporting information" href="urn-x:wiley:08853185:media:mds23221:MDS_23221_sm_suppinfo2"></mediaResource><caption>Supplementary_Material 2: Bead Studio Illumina plots for all autozygous segments detected by the Homozygosity detector plug‐in software within the Bead Studio program (Pink shadow, Illumina). The genetic defects identified in these autozygous segment and the chromosomal localization of ATP13A2, PLA2G6 and FBXO7 genes are shown in red.</caption></supportingInfoItem><supportingInfoItem><mediaResource alt="supporting information" href="urn-x:wiley:08853185:media:mds23221:MDS_23221_sm_suppvideo1"></mediaResource><caption>Supporting Video 1.</caption></supportingInfoItem><supportingInfoItem><mediaResource alt="supporting information" href="urn-x:wiley:08853185:media:mds23221:MDS_23221_sm_suppvideo2"></mediaResource><caption>Supporting Video 2.</caption></supportingInfoItem><supportingInfoItem><mediaResource alt="supporting information" href="urn-x:wiley:08853185:media:mds23221:MDS_23221_sm_suppvideo3"></mediaResource><caption>Supporting Video 3.</caption></supportingInfoItem><supportingInfoItem><mediaResource alt="supporting information" href="urn-x:wiley:08853185:media:mds23221:MDS_23221_sm_suppvideo4"></mediaResource><caption>Supporting Video 4.</caption></supportingInfoItem><supportingInfoItem><mediaResource alt="supporting information" href="urn-x:wiley:08853185:media:mds23221:MDS_23221_sm_suppvideo5"></mediaResource><caption>Supporting Video 5.</caption></supportingInfoItem><supportingInfoItem><mediaResource alt="supporting information" href="urn-x:wiley:08853185:media:mds23221:MDS_23221_sm_suppvideo6"></mediaResource><caption>Supporting Video 6.</caption></supportingInfoItem></supportingInformation><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><p>Seven autosomal recessive genes associated with juvenile and young‐onset Levodopa‐responsive parkinsonism have been identified. Mutations in <i>PRKN</i>, <i>DJ‐1</i>, and <i>PINK1</i> are associated with a rather pure parkinsonian phenotype, and have a more benign course with sustained treatment response and absence of dementia. On the other hand, Kufor‐Rakeb syndrome has additional signs, which distinguish it clearly from Parkinson's disease including supranuclear vertical gaze palsy, myoclonic jerks, pyramidal signs, and cognitive impairment. Neurodegeneration with brain iron accumulation type I (Hallervorden‐Spatz syndrome) due to mutations in <i>PANK2</i> gene may share similar features with Kufor‐Rakeb syndrome. Mutations in three other genes, <i>PLA2G6</i> (PARK14), <i>FBXO7</i> (PARK15), and Spatacsin (SPG11) also produce clinical similar phenotypes in that they presented with rapidly progressive parkinsonism, initially responsive to Levodopa treatment but later, developed additional features including cognitive decline and loss of Levodopa responsiveness. Here, using homozygosity mapping and sequence analysis in families with complex parkinsonisms, we identified genetic defects in the <i>ATP13A2</i> (1 family), <i>PLA2G6</i> (1 family) <i>FBXO7</i> (2 families), and SPG11 (1 family). The genetic heterogeneity was surprising given their initially common clinical features. On careful review, we found the <i>FBXO7</i> cases to have a phenotype more similar to PRKN gene associated parkinsonism. The <i>ATP13A2</i> and <i>PLA2G6</i> cases were more seriously disabled with additional swallowing problems, dystonic features, severe in some, and usually pyramidal involvement including pyramidal weakness. These data suggest that these four genes account for many cases of Levodopa responsive parkinsonism with pyramidal signs cases formerly categorized clinically as pallido‐pyramidal syndrome. © 2010 Movement Disorder Society.</p></abstract></abstractGroup></contentMeta><noteGroup><note xml:id="fn2"><p>Potential conflict of interest: Nothing to report.</p></note></noteGroup></header></component></istex:document></istex:metadataXml><!--Version 0.6 générée le 3-12-2015--><mods version="3.6"><titleInfo lang="en"><title>Early‐onset L‐dopa‐responsive parkinsonism with pyramidal signs due to ATP13A2, PLA2G6, FBXO7 and spatacsin mutations</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>Complex Recessive Parkinsonisms</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Early‐onset L‐dopa‐responsive parkinsonism with pyramidal signs due to</title></titleInfo><name type="personal"><namePart type="given">Coro</namePart><namePart 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type="termsOfAddress">MD</namePart><affiliation>Schilling Section of Clinical and Molecular Neurogenetics, Department of Neurology, University Luebeck, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Nin</namePart><namePart type="family">Bajaj</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neurology, Queens Medical Center, University of Nottingham, Nottingham, United Kingdom</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Murat</namePart><namePart type="family">Emre</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neurology, Behavioral Neurology and Movement Disorders Unit, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Andrew B.</namePart><namePart type="family">Singleton</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Mary Land, USA</affiliation><affiliation>Public Health Sciences and Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">John</namePart><namePart type="family">Hardy</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Department of Molecular Neuroscience and Reta Lila Weston Institute, UCL Institute of Neurology, London, Queen Square, London, United Kingdom</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Kailash P.</namePart><namePart type="family">Bhatia</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Schilling Section of Clinical and Molecular Neurogenetics, Department of Neurology, University Luebeck, Germany</affiliation><description>Correspondence: Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, Queen Square, London, United Kingdom, WCIN 3BG</description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Sebastian</namePart><namePart type="family">Brandner</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Division of Neuropathology, UCL Institute of Neurology, Queen Square, London WC1N 3BG, United Kingdom</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Andrew J.</namePart><namePart type="family">Lees</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Molecular Neuroscience and Reta Lila Weston Institute, UCL Institute of Neurology, London, Queen Square, London, United Kingdom</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Henry</namePart><namePart type="family">Houlden</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Molecular Neuroscience and Reta Lila Weston Institute, UCL Institute of Neurology, London, Queen Square, London, United Kingdom</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre authority="originalCategForm">article</genre><originInfo><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><place><placeTerm type="text">Hoboken</placeTerm></place><dateIssued encoding="w3cdtf">2010-09-15</dateIssued><dateCaptured encoding="w3cdtf">2010-01-18</dateCaptured><dateValid encoding="w3cdtf">2010-04-07</dateValid><copyrightDate encoding="w3cdtf">2010</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType><extent unit="figures">2</extent><extent unit="tables">2</extent><extent unit="references">39</extent><extent unit="words">6470</extent></physicalDescription><abstract lang="en">Seven autosomal recessive genes associated with juvenile and young‐onset Levodopa‐responsive parkinsonism have been identified. Mutations in PRKN, DJ‐1, and PINK1 are associated with a rather pure parkinsonian phenotype, and have a more benign course with sustained treatment response and absence of dementia. On the other hand, Kufor‐Rakeb syndrome has additional signs, which distinguish it clearly from Parkinson's disease including supranuclear vertical gaze palsy, myoclonic jerks, pyramidal signs, and cognitive impairment. Neurodegeneration with brain iron accumulation type I (Hallervorden‐Spatz syndrome) due to mutations in PANK2 gene may share similar features with Kufor‐Rakeb syndrome. Mutations in three other genes, PLA2G6 (PARK14), FBXO7 (PARK15), and Spatacsin (SPG11) also produce clinical similar phenotypes in that they presented with rapidly progressive parkinsonism, initially responsive to Levodopa treatment but later, developed additional features including cognitive decline and loss of Levodopa responsiveness. Here, using homozygosity mapping and sequence analysis in families with complex parkinsonisms, we identified genetic defects in the ATP13A2 (1 family), PLA2G6 (1 family) FBXO7 (2 families), and SPG11 (1 family). The genetic heterogeneity was surprising given their initially common clinical features. On careful review, we found the FBXO7 cases to have a phenotype more similar to PRKN gene associated parkinsonism. The ATP13A2 and PLA2G6 cases were more seriously disabled with additional swallowing problems, dystonic features, severe in some, and usually pyramidal involvement including pyramidal weakness. These data suggest that these four genes account for many cases of Levodopa responsive parkinsonism with pyramidal signs cases formerly categorized clinically as pallido‐pyramidal syndrome. © 2010 Movement Disorder Society.</abstract><note type="content">*Potential conflict of interest: Nothing to report.</note><subject lang="en"><genre>Keywords</genre><topic>parkinsonism</topic><topic>recessive</topic><topic>ATP13A2</topic><topic>PLA2G6</topic><topic>FBXO7</topic><topic>Spatacsin</topic></subject><relatedItem type="host"><titleInfo><title>Movement Disorders</title></titleInfo><titleInfo type="abbreviated"><title>Mov. Disord.</title></titleInfo><note type="content"> Additional Supporting Information may be found in the online version of this article.Supporting Info Item: Supplementary_Material 1: Genomic sequences of the primes employed to amplify the coding and intron‐exon boundaries of the ATP13A2, PLA2G6, FBXO7 and Spatacsin genes. - Supplementary_Material 2: Bead Studio Illumina plots for all autozygous segments detected by the Homozygosity detector plug‐in software within the Bead Studio program (Pink shadow, Illumina). The genetic defects identified in these autozygous segment and the chromosomal localization of ATP13A2, PLA2G6 and FBXO7 genes are shown in red. - Supporting Video 1. - Supporting Video 2. - Supporting Video 3. - Supporting Video 4. - Supporting Video 5. - Supporting Video 6. - </note><subject><genre>article category</genre><topic>Research Article</topic></subject><identifier type="ISSN">0885-3185</identifier><identifier type="eISSN">1531-8257</identifier><identifier type="DOI">10.1002/(ISSN)1531-8257</identifier><identifier type="PublisherID">MDS</identifier><part><date>2010</date><detail type="volume"><caption>vol.</caption><number>25</number></detail><detail type="issue"><caption>no.</caption><number>12</number></detail><extent unit="pages"><start>1791</start><end>1800</end><total>10</total></extent></part></relatedItem><identifier type="istex">2E3B8506FEF133B82EECBF1E333493CB60F5080E</identifier><identifier type="DOI">10.1002/mds.23221</identifier><identifier type="ArticleID">MDS23221</identifier><accessCondition type="use and reproduction" contentType="copyright">Copyright © 2010 Movement Disorder Society</accessCondition><recordInfo><recordOrigin>Wiley Subscription Services, Inc., A Wiley Company</recordOrigin><recordContentSource>WILEY</recordContentSource></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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|texte= Early‐onset L‐dopa‐responsive parkinsonism with pyramidal signs due to ATP13A2, PLA2G6, FBXO7 and spatacsin mutations
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