Genetic etiology of Parkinson disease associated with mutations in the SNCA, PARK2, PINK1, PARK7, and LRRK2 genes: a mutation update
Identifieur interne : 000185 ( Main/Corpus ); précédent : 000184; suivant : 000186Genetic etiology of Parkinson disease associated with mutations in the SNCA, PARK2, PINK1, PARK7, and LRRK2 genes: a mutation update
Auteurs : Karen Nuytemans ; Jessie Theuns ; Marc Cruts ; Christine Van BroeckhovenSource :
- Human Mutation [ 1059-7794 ] ; 2010-07.
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Abstract
To date, molecular genetic analyses have identified over 500 distinct DNA variants in five disease genes associated with familial Parkinson disease; α‐synuclein (SNCA), parkin (PARK2), PTEN‐induced putative kinase 1 (PINK1), DJ‐1 (PARK7), and Leucine‐rich repeat kinase 2 (LRRK2). These genetic variants include ∼82% simple mutations and ∼18% copy number variations. Some mutation subtypes are likely underestimated because only few studies reported extensive mutation analyses of all five genes, by both exonic sequencing and dosage analyses. Here we present an update of all mutations published to date in the literature, systematically organized in a novel mutation database (http://www.molgen.ua.ac.be/PDmutDB). In addition, we address the biological relevance of putative pathogenic mutations. This review emphasizes the need for comprehensive genetic screening of Parkinson patients followed by an insightful study of the functional relevance of observed genetic variants. Moreover, while capturing existing data from the literature it became apparent that several of the five Parkinson genes were also contributing to the genetic etiology of other Lewy Body Diseases and Parkinson‐plus syndromes, indicating that mutation screening is recommendable in these patient groups. Hum Mutat 31:763–780, 2010. © 2010 Wiley‐Liss, Inc.
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DOI: 10.1002/humu.21277
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Mutat.</title><idno type="ISSN">1059-7794</idno><idno type="eISSN">1098-1004</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2010-07">2010-07</date><biblScope unit="volume">31</biblScope><biblScope unit="issue">7</biblScope><biblScope unit="page" from="763">763</biblScope><biblScope unit="page" to="780">780</biblScope></imprint><idno type="ISSN">1059-7794</idno></series><idno type="istex">609453990A98DF9FAAC776388F4D998482A638C5</idno><idno type="DOI">10.1002/humu.21277</idno><idno type="ArticleID">HUMU21277</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">1059-7794</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>LRRK2</term><term>PARK2</term><term>PARK7</term><term>PINK1</term><term>Parkinson disease</term><term>SNCA</term><term>database</term><term>genetic etiology</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">To date, molecular genetic analyses have identified over 500 distinct DNA variants in five disease genes associated with familial Parkinson disease; α‐synuclein (SNCA), parkin (PARK2), PTEN‐induced putative kinase 1 (PINK1), DJ‐1 (PARK7), and Leucine‐rich repeat kinase 2 (LRRK2). These genetic variants include ∼82% simple mutations and ∼18% copy number variations. Some mutation subtypes are likely underestimated because only few studies reported extensive mutation analyses of all five genes, by both exonic sequencing and dosage analyses. Here we present an update of all mutations published to date in the literature, systematically organized in a novel mutation database (http://www.molgen.ua.ac.be/PDmutDB). In addition, we address the biological relevance of putative pathogenic mutations. This review emphasizes the need for comprehensive genetic screening of Parkinson patients followed by an insightful study of the functional relevance of observed genetic variants. Moreover, while capturing existing data from the literature it became apparent that several of the five Parkinson genes were also contributing to the genetic etiology of other Lewy Body Diseases and Parkinson‐plus syndromes, indicating that mutation screening is recommendable in these patient groups. Hum Mutat 31:763–780, 2010. © 2010 Wiley‐Liss, Inc.</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Karen Nuytemans</name><affiliations><json:string>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium</json:string><json:string>Laboratory of Neurogenetics, Institute Born‐Bunge, University of Antwerp, Antwerpen, Belgium</json:string></affiliations></json:item><json:item><name>Jessie Theuns</name><affiliations><json:string>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium</json:string><json:string>Laboratory of Neurogenetics, Institute Born‐Bunge, University of Antwerp, Antwerpen, Belgium</json:string></affiliations></json:item><json:item><name>Marc Cruts</name><affiliations><json:string>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium</json:string><json:string>Laboratory of Neurogenetics, Institute Born‐Bunge, University of Antwerp, Antwerpen, Belgium</json:string></affiliations></json:item><json:item><name>Christine Van Broeckhoven</name><affiliations><json:string>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium</json:string><json:string>Laboratory of Neurogenetics, Institute Born‐Bunge, University of Antwerp, Antwerpen, Belgium</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>Parkinson disease</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>genetic etiology</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>database</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>SNCA</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>PARK2</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>PINK1</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>PARK7</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>LRRK2</value></json:item></subject><articleId><json:string>HUMU21277</json:string></articleId><language><json:string>eng</json:string></language><abstract>To date, molecular genetic analyses have identified over 500 distinct DNA variants in five disease genes associated with familial Parkinson disease; α‐synuclein (SNCA), parkin (PARK2), PTEN‐induced putative kinase 1 (PINK1), DJ‐1 (PARK7), and Leucine‐rich repeat kinase 2 (LRRK2). These genetic variants include ∼82% simple mutations and ∼18% copy number variations. Some mutation subtypes are likely underestimated because only few studies reported extensive mutation analyses of all five genes, by both exonic sequencing and dosage analyses. Here we present an update of all mutations published to date in the literature, systematically organized in a novel mutation database (http://www.molgen.ua.ac.be/PDmutDB). In addition, we address the biological relevance of putative pathogenic mutations. This review emphasizes the need for comprehensive genetic screening of Parkinson patients followed by an insightful study of the functional relevance of observed genetic variants. Moreover, while capturing existing data from the literature it became apparent that several of the five Parkinson genes were also contributing to the genetic etiology of other Lewy Body Diseases and Parkinson‐plus syndromes, indicating that mutation screening is recommendable in these patient groups. 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H. Cotton</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Genetic etiology of Parkinson disease associated with mutations in the SNCA, PARK2, PINK1, PARK7, and LRRK2 genes: a mutation update</title><author><persName><forename type="first">Karen</forename><surname>Nuytemans</surname></persName><affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium</affiliation><affiliation>Laboratory of Neurogenetics, Institute Born‐Bunge, University of Antwerp, Antwerpen, Belgium</affiliation></author><author><persName><forename type="first">Jessie</forename><surname>Theuns</surname></persName><affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium</affiliation><affiliation>Laboratory of Neurogenetics, Institute Born‐Bunge, University of Antwerp, Antwerpen, Belgium</affiliation></author><author><persName><forename type="first">Marc</forename><surname>Cruts</surname></persName><affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium</affiliation><affiliation>Laboratory of Neurogenetics, Institute Born‐Bunge, University of Antwerp, Antwerpen, Belgium</affiliation></author><author><persName><forename type="first">Christine</forename><surname>Van Broeckhoven</surname></persName><note type="correspondence"><p>Correspondence: Neurodegenerative Brain Diseases Group, VIB, Department of Molecular Genetics, University of Antwerp, CDE, Universiteitsplein 1, B‐2610 Antwerpen, Belgium</p></note><affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium</affiliation><affiliation>Laboratory of Neurogenetics, Institute Born‐Bunge, University of Antwerp, Antwerpen, Belgium</affiliation></author></analytic><monogr><title level="j">Human Mutation</title><title level="j" type="abbrev">Hum. Mutat.</title><idno type="pISSN">1059-7794</idno><idno type="eISSN">1098-1004</idno><idno type="DOI">10.1002/(ISSN)1098-1004</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2010-07"></date><biblScope unit="volume">31</biblScope><biblScope unit="issue">7</biblScope><biblScope unit="page" from="763">763</biblScope><biblScope unit="page" to="780">780</biblScope></imprint></monogr><idno type="istex">609453990A98DF9FAAC776388F4D998482A638C5</idno><idno type="DOI">10.1002/humu.21277</idno><idno type="ArticleID">HUMU21277</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2010</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>To date, molecular genetic analyses have identified over 500 distinct DNA variants in five disease genes associated with familial Parkinson disease; α‐synuclein (SNCA), parkin (PARK2), PTEN‐induced putative kinase 1 (PINK1), DJ‐1 (PARK7), and Leucine‐rich repeat kinase 2 (LRRK2). These genetic variants include ∼82% simple mutations and ∼18% copy number variations. Some mutation subtypes are likely underestimated because only few studies reported extensive mutation analyses of all five genes, by both exonic sequencing and dosage analyses. Here we present an update of all mutations published to date in the literature, systematically organized in a novel mutation database (http://www.molgen.ua.ac.be/PDmutDB). In addition, we address the biological relevance of putative pathogenic mutations. This review emphasizes the need for comprehensive genetic screening of Parkinson patients followed by an insightful study of the functional relevance of observed genetic variants. Moreover, while capturing existing data from the literature it became apparent that several of the five Parkinson genes were also contributing to the genetic etiology of other Lewy Body Diseases and Parkinson‐plus syndromes, indicating that mutation screening is recommendable in these patient groups. Hum Mutat 31:763–780, 2010. © 2010 Wiley‐Liss, Inc.</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Keywords</head><item><term>Parkinson disease</term></item><item><term>genetic etiology</term></item><item><term>database</term></item><item><term>SNCA</term></item><item><term>PARK2</term></item><item><term>PINK1</term></item><item><term>PARK7</term></item><item><term>LRRK2</term></item></list></keywords></textClass><textClass><keywords scheme="Journal Subject"><list><head>article category</head><item><term>Mutation Update</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2010-02-12">Received</change><change when="2010-04-21">Registration</change><change when="2010-07">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/609453990A98DF9FAAC776388F4D998482A638C5/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)1098-1004</doi><issn type="print">1059-7794</issn><issn type="electronic">1098-1004</issn><idGroup><id type="product" value="HUMU"></id></idGroup><titleGroup><title type="main" xml:lang="en" sort="HUMAN MUTATION">Human Mutation</title><title type="short">Hum. 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These genetic variants include ∼82% simple mutations and ∼18% copy number variations. Some mutation subtypes are likely underestimated because only few studies reported extensive mutation analyses of all five genes, by both exonic sequencing and dosage analyses. Here we present an update of all mutations published to date in the literature, systematically organized in a novel mutation database (<url href="http://www.molgen.ua.ac.be/PDmutDB">http://www.molgen.ua.ac.be/PDmutDB</url>). In addition, we address the biological relevance of putative pathogenic mutations. This review emphasizes the need for comprehensive genetic screening of Parkinson patients followed by an insightful study of the functional relevance of observed genetic variants. Moreover, while capturing existing data from the literature it became apparent that several of the five Parkinson genes were also contributing to the genetic etiology of other Lewy Body Diseases and Parkinson‐plus syndromes, indicating that mutation screening is recommendable in these patient groups. Hum Mutat 31:763–780, 2010. © 2010 Wiley‐Liss, Inc.</p></abstract></abstractGroup></contentMeta><noteGroup><note xml:id="fn1"><p>Communicated by Richard G. H. Cotton</p></note></noteGroup></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Genetic etiology of Parkinson disease associated with mutations in the SNCA, PARK2, PINK1, PARK7, and LRRK2 genes: a mutation update</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Genetic etiology of Parkinson disease associated with mutations in the</title></titleInfo><name type="personal"><namePart type="given">Karen</namePart><namePart type="family">Nuytemans</namePart><affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium</affiliation><affiliation>Laboratory of Neurogenetics, Institute Born‐Bunge, University of Antwerp, Antwerpen, Belgium</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jessie</namePart><namePart type="family">Theuns</namePart><affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium</affiliation><affiliation>Laboratory of Neurogenetics, Institute Born‐Bunge, University of Antwerp, Antwerpen, Belgium</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Marc</namePart><namePart type="family">Cruts</namePart><affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium</affiliation><affiliation>Laboratory of Neurogenetics, Institute Born‐Bunge, University of Antwerp, Antwerpen, Belgium</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Christine</namePart><namePart type="family">Van Broeckhoven</namePart><affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium</affiliation><affiliation>Laboratory of Neurogenetics, Institute Born‐Bunge, University of Antwerp, Antwerpen, Belgium</affiliation><description>Correspondence: Neurodegenerative Brain Diseases Group, VIB, Department of Molecular Genetics, University of Antwerp, CDE, Universiteitsplein 1, B‐2610 Antwerpen, Belgium</description><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="other" displayLabel="miscellaneous"></genre><originInfo><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><place><placeTerm type="text">Hoboken</placeTerm></place><dateIssued encoding="w3cdtf">2010-07</dateIssued><dateCaptured encoding="w3cdtf">2010-02-12</dateCaptured><dateValid encoding="w3cdtf">2010-04-21</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">5</extent><extent unit="tables">5</extent><extent unit="references">313</extent></physicalDescription><abstract lang="en">To date, molecular genetic analyses have identified over 500 distinct DNA variants in five disease genes associated with familial Parkinson disease; α‐synuclein (SNCA), parkin (PARK2), PTEN‐induced putative kinase 1 (PINK1), DJ‐1 (PARK7), and Leucine‐rich repeat kinase 2 (LRRK2). These genetic variants include ∼82% simple mutations and ∼18% copy number variations. Some mutation subtypes are likely underestimated because only few studies reported extensive mutation analyses of all five genes, by both exonic sequencing and dosage analyses. Here we present an update of all mutations published to date in the literature, systematically organized in a novel mutation database (http://www.molgen.ua.ac.be/PDmutDB). In addition, we address the biological relevance of putative pathogenic mutations. This review emphasizes the need for comprehensive genetic screening of Parkinson patients followed by an insightful study of the functional relevance of observed genetic variants. Moreover, while capturing existing data from the literature it became apparent that several of the five Parkinson genes were also contributing to the genetic etiology of other Lewy Body Diseases and Parkinson‐plus syndromes, indicating that mutation screening is recommendable in these patient groups. Hum Mutat 31:763–780, 2010. © 2010 Wiley‐Liss, Inc.</abstract><note type="content">*Communicated by Richard G. H. Cotton</note><subject lang="en"><genre>Keywords</genre><topic>Parkinson disease</topic><topic>genetic etiology</topic><topic>database</topic><topic>SNCA</topic><topic>PARK2</topic><topic>PINK1</topic><topic>PARK7</topic><topic>LRRK2</topic></subject><relatedItem type="host"><titleInfo><title>Human Mutation</title></titleInfo><titleInfo type="abbreviated"><title>Hum. Mutat.</title></titleInfo><genre type="Journal">journal</genre><note type="content"> Additional Supporting Information may be found in the online version of this article.Supporting Info Item: Supporting Information - </note><subject><genre>article category</genre><topic>Mutation Update</topic></subject><identifier type="ISSN">1059-7794</identifier><identifier type="eISSN">1098-1004</identifier><identifier type="DOI">10.1002/(ISSN)1098-1004</identifier><identifier type="PublisherID">HUMU</identifier><part><date>2010</date><detail type="volume"><caption>vol.</caption><number>31</number></detail><detail type="issue"><caption>no.</caption><number>7</number></detail><extent unit="pages"><start>763</start><end>780</end><total>18</total></extent></part></relatedItem><identifier type="istex">609453990A98DF9FAAC776388F4D998482A638C5</identifier><identifier type="DOI">10.1002/humu.21277</identifier><identifier type="ArticleID">HUMU21277</identifier><accessCondition type="use and reproduction" contentType="copyright">© 2010 Wiley‐Liss, Inc.</accessCondition><recordInfo><recordContentSource>WILEY</recordContentSource><recordOrigin>Wiley Subscription Services, Inc., A Wiley Company</recordOrigin></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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