R1514Q substitution in Lrrk2 is not a pathogenic Parkinson's disease mutation
Identifieur interne : 001119 ( Main/Corpus ); précédent : 001118; suivant : 001120R1514Q substitution in Lrrk2 is not a pathogenic Parkinson's disease mutation
Auteurs : William C. Nichols ; Diane K. Marek ; Michael W. Pauciulo ; Nathan Pankratz ; Cheryl A. Halter ; Alice Rudolph ; Clifford W. Shults ; Joanne Wojcieszek ; Tatiana ForoudSource :
- Movement Disorders [ 0885-3185 ] ; 2007-01-15.
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- KwdEn :
Abstract
Mutations in LRRK2 were first reported as causing Parkinson's disease (PD) in late 2004. Since then, approximately a dozen LRRK2 substitutions have been identified that are believed to be pathogenic mutations. The substitution of adenine for guanine at nucleotide 4541 (4541G>A) in LRRK2 was recently reported. This substitution resulted in the replacement of an arginine at position 1514 with a glutamine (R1514Q). Although this substitution was not found in a large cohort of controls, its pathogenicity could not be verified. We have now genotyped the R1514Q substitution in a sample of 954 PD patients from 429 multiplex PD families. This substitution was identified in 1.8% of the PD patients; however, the majority of the PD sibships segregating this substitution were discordant for this putative mutation. In addition, the R1514Q substitution was detected in 1.4% of neurologically evaluated, control individuals. These data suggest that the R1514Q variant is not a pathogenic LRRK2 mutation. We believe it is imperative that the causative nature of any newly identified genetic variant be determined before it is included in any panel for diagnostic testing. © 2006 Movement Disorder Society
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DOI: 10.1002/mds.21233
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Marek</name><affiliation><mods:affiliation>Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA</mods:affiliation></affiliation></author><author><name sortKey="Pauciulo, Michael W" sort="Pauciulo, Michael W" uniqKey="Pauciulo M" first="Michael W." last="Pauciulo">Michael W. Pauciulo</name><affiliation><mods:affiliation>Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA</mods:affiliation></affiliation></author><author><name sortKey="Pankratz, Nathan" sort="Pankratz, Nathan" uniqKey="Pankratz N" first="Nathan" last="Pankratz">Nathan Pankratz</name><affiliation><mods:affiliation>Indiana University Medical Center, Indianapolis, Indiana, USA</mods:affiliation></affiliation></author><author><name sortKey="Halter, Cheryl A" sort="Halter, Cheryl A" uniqKey="Halter C" first="Cheryl A." last="Halter">Cheryl A. 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Nichols</name><affiliation><mods:affiliation>Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>University of Cincinnati College of Medicine, Cincinnati, Ohio, USA</mods:affiliation></affiliation></author><author><name sortKey="Marek, Diane K" sort="Marek, Diane K" uniqKey="Marek D" first="Diane K." last="Marek">Diane K. Marek</name><affiliation><mods:affiliation>Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA</mods:affiliation></affiliation></author><author><name sortKey="Pauciulo, Michael W" sort="Pauciulo, Michael W" uniqKey="Pauciulo M" first="Michael W." last="Pauciulo">Michael W. 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Halter</name><affiliation><mods:affiliation>Indiana University Medical Center, Indianapolis, Indiana, USA</mods:affiliation></affiliation></author><author><name sortKey="Rudolph, Alice" sort="Rudolph, Alice" uniqKey="Rudolph A" first="Alice" last="Rudolph">Alice Rudolph</name><affiliation><mods:affiliation>University of Rochester, Rochester, New York, USA</mods:affiliation></affiliation></author><author><name sortKey="Shults, Clifford W" sort="Shults, Clifford W" uniqKey="Shults C" first="Clifford W." last="Shults">Clifford W. Shults</name><affiliation><mods:affiliation>University of California, San Diego, La Jolla, and VA San Diego Healthcare System, San Diego, California, USA</mods:affiliation></affiliation></author><author><name sortKey="Wojcieszek, Joanne" sort="Wojcieszek, Joanne" uniqKey="Wojcieszek J" first="Joanne" last="Wojcieszek">Joanne Wojcieszek</name><affiliation><mods:affiliation>Indiana University Medical Center, Indianapolis, Indiana, USA</mods:affiliation></affiliation></author><author><name sortKey="Foroud, Tatiana" sort="Foroud, Tatiana" uniqKey="Foroud T" first="Tatiana" last="Foroud">Tatiana Foroud</name><affiliation><mods:affiliation>Indiana University Medical Center, Indianapolis, Indiana, USA</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Movement Disorders</title><title level="j" type="sub">Official Journal of the Movement Disorder Society</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="2007-01-15">2007-01-15</date><biblScope unit="volume">22</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="254">254</biblScope><biblScope unit="page" to="256">256</biblScope></imprint><idno type="ISSN">0885-3185</idno></series><idno type="istex">24667288E607E12E0690311F4A6AA62235686E9D</idno><idno type="DOI">10.1002/mds.21233</idno><idno type="ArticleID">MDS21233</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0885-3185</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>LRRK2</term><term>Parkinson's disease</term><term>genetics</term><term>mutation</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Mutations in LRRK2 were first reported as causing Parkinson's disease (PD) in late 2004. Since then, approximately a dozen LRRK2 substitutions have been identified that are believed to be pathogenic mutations. The substitution of adenine for guanine at nucleotide 4541 (4541G>A) in LRRK2 was recently reported. This substitution resulted in the replacement of an arginine at position 1514 with a glutamine (R1514Q). Although this substitution was not found in a large cohort of controls, its pathogenicity could not be verified. We have now genotyped the R1514Q substitution in a sample of 954 PD patients from 429 multiplex PD families. This substitution was identified in 1.8% of the PD patients; however, the majority of the PD sibships segregating this substitution were discordant for this putative mutation. In addition, the R1514Q substitution was detected in 1.4% of neurologically evaluated, control individuals. These data suggest that the R1514Q variant is not a pathogenic LRRK2 mutation. We believe it is imperative that the causative nature of any newly identified genetic variant be determined before it is included in any panel for diagnostic testing. © 2006 Movement Disorder Society</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>William C. Nichols PhD</name><affiliations><json:string>Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA</json:string><json:string>University of Cincinnati College of Medicine, Cincinnati, Ohio, USA</json:string></affiliations></json:item><json:item><name>Diane K. Marek BS</name><affiliations><json:string>Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA</json:string></affiliations></json:item><json:item><name>Michael W. Pauciulo MBA</name><affiliations><json:string>Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA</json:string></affiliations></json:item><json:item><name>Nathan Pankratz PhD</name><affiliations><json:string>Indiana University Medical Center, Indianapolis, Indiana, USA</json:string></affiliations></json:item><json:item><name>Cheryl A. Halter MS</name><affiliations><json:string>Indiana University Medical Center, Indianapolis, Indiana, USA</json:string></affiliations></json:item><json:item><name>Alice Rudolph PhD</name><affiliations><json:string>University of Rochester, Rochester, New York, USA</json:string></affiliations></json:item><json:item><name>Clifford W. Shults MD</name><affiliations><json:string>University of California, San Diego, La Jolla, and VA San Diego Healthcare System, San Diego, California, USA</json:string></affiliations></json:item><json:item><name>Joanne Wojcieszek MD</name><affiliations><json:string>Indiana University Medical Center, Indianapolis, Indiana, USA</json:string></affiliations></json:item><json:item><name>Tatiana Foroud PhD</name><affiliations><json:string>Indiana University Medical Center, Indianapolis, Indiana, USA</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>Parkinson's disease</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>genetics</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>LRRK2</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>mutation</value></json:item></subject><articleId><json:string>MDS21233</json:string></articleId><language><json:string>eng</json:string></language><abstract>Mutations in LRRK2 were first reported as causing Parkinson's disease (PD) in late 2004. Since then, approximately a dozen LRRK2 substitutions have been identified that are believed to be pathogenic mutations. The substitution of adenine for guanine at nucleotide 4541 (4541G>A) in LRRK2 was recently reported. This substitution resulted in the replacement of an arginine at position 1514 with a glutamine (R1514Q). Although this substitution was not found in a large cohort of controls, its pathogenicity could not be verified. We have now genotyped the R1514Q substitution in a sample of 954 PD patients from 429 multiplex PD families. This substitution was identified in 1.8% of the PD patients; however, the majority of the PD sibships segregating this substitution were discordant for this putative mutation. In addition, the R1514Q substitution was detected in 1.4% of neurologically evaluated, control individuals. These data suggest that the R1514Q variant is not a pathogenic LRRK2 mutation. We believe it is imperative that the causative nature of any newly identified genetic variant be determined before it is included in any panel for diagnostic testing. © 2006 Movement Disorder Society</abstract><qualityIndicators><score>5.261</score><pdfVersion>1.3</pdfVersion><pdfPageSize>594 x 792 pts</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>4</keywordCount><abstractCharCount>1200</abstractCharCount><pdfWordCount>3053</pdfWordCount><pdfCharCount>19486</pdfCharCount><pdfPageCount>4</pdfPageCount><abstractWordCount>184</abstractWordCount></qualityIndicators><title>R1514Q substitution in Lrrk2 is not a pathogenic Parkinson's disease mutation</title><genre><json:string>article</json:string></genre><host><volume>22</volume><publisherId><json:string>MDS</json:string></publisherId><pages><total>3</total><last>256</last><first>254</first></pages><issn><json:string>0885-3185</json:string></issn><issue>2</issue><subject><json:item><value>Brief Report</value></json:item></subject><genre><json:string>Journal</json:string></genre><language><json:string>unknown</json:string></language><eissn><json:string>1531-8257</json:string></eissn><title>Movement Disorders</title><doi><json:string>10.1002/(ISSN)1531-8257</json:string></doi></host><publicationDate>2007</publicationDate><copyrightDate>2007</copyrightDate><doi><json:string>10.1002/mds.21233</json:string></doi><id>24667288E607E12E0690311F4A6AA62235686E9D</id><fulltext><json:item><original>true</original><mimetype>application/pdf</mimetype><extension>pdf</extension><uri>https://api.istex.fr/document/24667288E607E12E0690311F4A6AA62235686E9D/fulltext/pdf</uri></json:item><json:item><original>false</original><mimetype>application/zip</mimetype><extension>zip</extension><uri>https://api.istex.fr/document/24667288E607E12E0690311F4A6AA62235686E9D/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/24667288E607E12E0690311F4A6AA62235686E9D/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">R1514Q substitution in Lrrk2 is not a pathogenic Parkinson's disease mutation</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><availability><p>WILEY</p></availability><date>2007</date></publicationStmt><notesStmt><note>Unknown funding agency - No. R01 NS37167;</note><note>National Cell Repository for Alzheimer's Disease - No. U24 AG021886;</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">R1514Q substitution in Lrrk2 is not a pathogenic Parkinson's disease mutation</title><author><persName><forename type="first">William C.</forename><surname>Nichols</surname></persName><roleName type="degree">PhD</roleName><note type="correspondence"><p>Correspondence: Division of Human Genetics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229</p></note><affiliation>Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA</affiliation><affiliation>University of Cincinnati College of Medicine, Cincinnati, Ohio, USA</affiliation></author><author><persName><forename type="first">Diane K.</forename><surname>Marek</surname></persName><roleName type="degree">BS</roleName><affiliation>Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA</affiliation></author><author><persName><forename type="first">Michael W.</forename><surname>Pauciulo</surname></persName><roleName type="degree">MBA</roleName><affiliation>Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA</affiliation></author><author><persName><forename type="first">Nathan</forename><surname>Pankratz</surname></persName><roleName type="degree">PhD</roleName><affiliation>Indiana University Medical Center, Indianapolis, Indiana, USA</affiliation></author><author><persName><forename type="first">Cheryl A.</forename><surname>Halter</surname></persName><roleName type="degree">MS</roleName><affiliation>Indiana University Medical Center, Indianapolis, Indiana, USA</affiliation></author><author><persName><forename type="first">Alice</forename><surname>Rudolph</surname></persName><roleName type="degree">PhD</roleName><affiliation>University of Rochester, Rochester, New York, USA</affiliation></author><author><persName><forename type="first">Clifford W.</forename><surname>Shults</surname></persName><roleName type="degree">MD</roleName><affiliation>University of California, San Diego, La Jolla, and VA San Diego Healthcare System, San Diego, California, USA</affiliation></author><author><persName><forename type="first">Joanne</forename><surname>Wojcieszek</surname></persName><roleName type="degree">MD</roleName><affiliation>Indiana University Medical Center, Indianapolis, Indiana, USA</affiliation></author><author><persName><forename type="first">Tatiana</forename><surname>Foroud</surname></persName><roleName type="degree">PhD</roleName><affiliation>Indiana University Medical Center, Indianapolis, Indiana, USA</affiliation></author></analytic><monogr><title level="j">Movement Disorders</title><title level="j" type="sub">Official Journal of the Movement Disorder Society</title><title level="j" type="abbrev">Mov. 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Since then, approximately a dozen LRRK2 substitutions have been identified that are believed to be pathogenic mutations. The substitution of adenine for guanine at nucleotide 4541 (4541G>A) in LRRK2 was recently reported. This substitution resulted in the replacement of an arginine at position 1514 with a glutamine (R1514Q). Although this substitution was not found in a large cohort of controls, its pathogenicity could not be verified. We have now genotyped the R1514Q substitution in a sample of 954 PD patients from 429 multiplex PD families. This substitution was identified in 1.8% of the PD patients; however, the majority of the PD sibships segregating this substitution were discordant for this putative mutation. In addition, the R1514Q substitution was detected in 1.4% of neurologically evaluated, control individuals. These data suggest that the R1514Q variant is not a pathogenic LRRK2 mutation. We believe it is imperative that the causative nature of any newly identified genetic variant be determined before it is included in any panel for diagnostic testing. © 2006 Movement Disorder Society</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Keywords</head><item><term>Parkinson's disease</term></item><item><term>genetics</term></item><item><term>LRRK2</term></item><item><term>mutation</term></item></list></keywords></textClass><textClass><keywords scheme="Journal Subject"><list><head>article category</head><item><term>Brief Report</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2006-04-24">Received</change><change when="2006-08-10">Registration</change><change when="2007-01-15">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/24667288E607E12E0690311F4A6AA62235686E9D/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="subtitle">Official Journal of the Movement Disorder Society</title><title type="short">Mov. 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K.</givenNames><familyName>Marek</familyName><degrees>BS</degrees></personName></creator><creator xml:id="au3" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Michael W.</givenNames><familyName>Pauciulo</familyName><degrees>MBA</degrees></personName></creator><creator xml:id="au4" creatorRole="author" affiliationRef="#af3"><personName><givenNames>Nathan</givenNames><familyName>Pankratz</familyName><degrees>PhD</degrees></personName></creator><creator xml:id="au5" creatorRole="author" affiliationRef="#af3"><personName><givenNames>Cheryl A.</givenNames><familyName>Halter</familyName><degrees>MS</degrees></personName></creator><creator xml:id="au6" creatorRole="author" affiliationRef="#af4"><personName><givenNames>Alice</givenNames><familyName>Rudolph</familyName><degrees>PhD</degrees></personName></creator><creator xml:id="au7" creatorRole="author" affiliationRef="#af5"><personName><givenNames>Clifford W.</givenNames><familyName>Shults</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au8" creatorRole="author" affiliationRef="#af3"><personName><givenNames>Joanne</givenNames><familyName>Wojcieszek</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au9" creatorRole="author" affiliationRef="#af3"><personName><givenNames>Tatiana</givenNames><familyName>Foroud</familyName><degrees>PhD</degrees></personName></creator></creators><affiliationGroup><affiliation xml:id="af1" countryCode="US" type="organization"><unparsedAffiliation>Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA</unparsedAffiliation></affiliation><affiliation xml:id="af2" countryCode="US" type="organization"><unparsedAffiliation>University of Cincinnati College of Medicine, Cincinnati, Ohio, USA</unparsedAffiliation></affiliation><affiliation xml:id="af3" countryCode="US" type="organization"><unparsedAffiliation>Indiana University Medical Center, Indianapolis, Indiana, USA</unparsedAffiliation></affiliation><affiliation xml:id="af4" countryCode="US" type="organization"><unparsedAffiliation>University of Rochester, Rochester, New York, USA</unparsedAffiliation></affiliation><affiliation xml:id="af5" countryCode="US" type="organization"><unparsedAffiliation>University of California, San Diego, La Jolla, and VA San Diego Healthcare System, San Diego, California, USA</unparsedAffiliation></affiliation></affiliationGroup><keywordGroup xml:lang="en" type="author"><keyword xml:id="kwd1">Parkinson's disease</keyword><keyword xml:id="kwd2">genetics</keyword><keyword xml:id="kwd3">LRRK2</keyword><keyword xml:id="kwd4">mutation</keyword></keywordGroup><fundingInfo><fundingAgency>Unknown funding agency</fundingAgency><fundingNumber>R01 NS37167</fundingNumber></fundingInfo><fundingInfo><fundingAgency>National Cell Repository for Alzheimer's Disease</fundingAgency><fundingNumber>U24 AG021886</fundingNumber></fundingInfo><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><p>Mutations in <i>LRRK2</i> were first reported as causing Parkinson's disease (PD) in late 2004. Since then, approximately a dozen <i>LRRK2</i> substitutions have been identified that are believed to be pathogenic mutations. The substitution of adenine for guanine at nucleotide 4541 (4541G>A) in <i>LRRK2</i> was recently reported. This substitution resulted in the replacement of an arginine at position 1514 with a glutamine (R1514Q). Although this substitution was not found in a large cohort of controls, its pathogenicity could not be verified. We have now genotyped the R1514Q substitution in a sample of 954 PD patients from 429 multiplex PD families. This substitution was identified in 1.8% of the PD patients; however, the majority of the PD sibships segregating this substitution were discordant for this putative mutation. In addition, the R1514Q substitution was detected in 1.4% of neurologically evaluated, control individuals. These data suggest that the R1514Q variant is not a pathogenic <i>LRRK2</i> mutation. We believe it is imperative that the causative nature of any newly identified genetic variant be determined before it is included in any panel for diagnostic testing. © 2006 Movement Disorder Society</p></abstract></abstractGroup></contentMeta></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>R1514Q substitution in Lrrk2 is not a pathogenic Parkinson's disease mutation</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>R1514Q Substitution in Lrrk2 is not a PD Mutation</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>R1514Q substitution in Lrrk2 is not a pathogenic Parkinson's disease mutation</title></titleInfo><name type="personal"><namePart type="given">William C.</namePart><namePart type="family">Nichols</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA</affiliation><affiliation>University of Cincinnati College of Medicine, Cincinnati, Ohio, USA</affiliation><description>Correspondence: Division of Human Genetics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229</description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Diane K.</namePart><namePart type="family">Marek</namePart><namePart type="termsOfAddress">BS</namePart><affiliation>Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Michael W.</namePart><namePart type="family">Pauciulo</namePart><namePart type="termsOfAddress">MBA</namePart><affiliation>Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Nathan</namePart><namePart type="family">Pankratz</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Indiana University Medical Center, Indianapolis, Indiana, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Cheryl A.</namePart><namePart type="family">Halter</namePart><namePart type="termsOfAddress">MS</namePart><affiliation>Indiana University Medical Center, Indianapolis, Indiana, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Alice</namePart><namePart type="family">Rudolph</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>University of Rochester, Rochester, New York, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Clifford W.</namePart><namePart type="family">Shults</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>University of California, San Diego, La Jolla, and VA San Diego Healthcare System, San Diego, California, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Joanne</namePart><namePart type="family">Wojcieszek</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Indiana University Medical Center, Indianapolis, Indiana, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Tatiana</namePart><namePart type="family">Foroud</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Indiana University Medical Center, Indianapolis, Indiana, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="article" displayLabel="article"></genre><originInfo><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><place><placeTerm type="text">Hoboken</placeTerm></place><dateIssued encoding="w3cdtf">2007-01-15</dateIssued><dateCaptured encoding="w3cdtf">2006-04-24</dateCaptured><dateValid encoding="w3cdtf">2006-08-10</dateValid><copyrightDate encoding="w3cdtf">2007</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="references">10</extent><extent unit="words">2616</extent></physicalDescription><abstract lang="en">Mutations in LRRK2 were first reported as causing Parkinson's disease (PD) in late 2004. Since then, approximately a dozen LRRK2 substitutions have been identified that are believed to be pathogenic mutations. The substitution of adenine for guanine at nucleotide 4541 (4541G>A) in LRRK2 was recently reported. This substitution resulted in the replacement of an arginine at position 1514 with a glutamine (R1514Q). Although this substitution was not found in a large cohort of controls, its pathogenicity could not be verified. We have now genotyped the R1514Q substitution in a sample of 954 PD patients from 429 multiplex PD families. This substitution was identified in 1.8% of the PD patients; however, the majority of the PD sibships segregating this substitution were discordant for this putative mutation. In addition, the R1514Q substitution was detected in 1.4% of neurologically evaluated, control individuals. These data suggest that the R1514Q variant is not a pathogenic LRRK2 mutation. We believe it is imperative that the causative nature of any newly identified genetic variant be determined before it is included in any panel for diagnostic testing. © 2006 Movement Disorder Society</abstract><note type="funding">Unknown funding agency - No. R01 NS37167; </note><note type="funding">National Cell Repository for Alzheimer's Disease - No. U24 AG021886; </note><subject lang="en"><genre>Keywords</genre><topic>Parkinson's disease</topic><topic>genetics</topic><topic>LRRK2</topic><topic>mutation</topic></subject><relatedItem type="host"><titleInfo><title>Movement Disorders</title><subTitle>Official Journal of the Movement Disorder Society</subTitle></titleInfo><titleInfo type="abbreviated"><title>Mov. Disord.</title></titleInfo><genre type="Journal">journal</genre><subject><genre>article category</genre><topic>Brief Report</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>2007</date><detail type="volume"><caption>vol.</caption><number>22</number></detail><detail type="issue"><caption>no.</caption><number>2</number></detail><extent unit="pages"><start>254</start><end>256</end><total>3</total></extent></part></relatedItem><identifier type="istex">24667288E607E12E0690311F4A6AA62235686E9D</identifier><identifier type="DOI">10.1002/mds.21233</identifier><identifier type="ArticleID">MDS21233</identifier><accessCondition type="use and reproduction" contentType="copyright">Copyright © 2006 Movement Disorder Society</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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