The curious case of phenocopies in families with genetic Parkinson's disease
Identifieur interne : 000254 ( Main/Corpus ); précédent : 000253; suivant : 000255The curious case of phenocopies in families with genetic Parkinson's disease
Auteurs : Christine Klein ; Rosalind Chuang ; Connie Marras ; Anthony E. LangSource :
- Movement Disorders [ 0885-3185 ] ; 2011-08-15.
English descriptors
Abstract
Monogenic forms of Parkinson's disease account for ∼3% of all “idiopathic” Parkinson's disease. With reduced penetrance in dominant forms and manifesting heterozygotes in recessive forms of Parkinson's disease, it has been well recognized that inheritance patterns do not always follow classic Mendelian genetics. A novel twist to the puzzle is the presence of phenocopies (i.e., family members with the same clinical syndrome as the mutation carriers, but lacking the familial mutation). We reviewed all pedigrees published between 1997 and 2009 with α‐synuclein, leucine‐rich repeat kinase 2, Parkin, or PTEN‐induced kinase 1 mutations with at least 2 affected individuals and known genetic status for the possible presence of phenocopies. Of 537 patients with clinical Parkinson's disease in 160 families meeting our inclusion criteria, 27 patients (5.0%) from 23 families (14.4%) were phenocopies. Phenocopies represented 3.8% of all blood relatives reported in the pedigrees containing phenocopies and an estimated 1.3% of all blood relatives in all pedigrees included. Both of these rates exceeded age‐specific prevalences of Parkinson's disease. In 4 families, the phenocopy was explained by another known mutation: In 2 pedigrees, a monogenic cause was likely; in another 2, secondary parkinsonism was suspected; and in the remaining 15 families, “sporadic Parkinson's disease” was suggested as the cause of disease in the phenocopy. The unexpectedly high number of phenocopies of mostly unknown origin within families with a seemingly known etiology of Parkinson's disease adds another level of complexity to genetic research of Parkinson's disease, as well as to the interpretation of genetic testing results in the clinical diagnostic setting. © 2011 Movement Disorder Society
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DOI: 10.1002/mds.23853
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ISTEX:10F7DC2554AD726CEEC38E30A5DF956F24D82293Le document en format XML
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With reduced penetrance in dominant forms and manifesting heterozygotes in recessive forms of Parkinson's disease, it has been well recognized that inheritance patterns do not always follow classic Mendelian genetics. A novel twist to the puzzle is the presence of phenocopies (i.e., family members with the same clinical syndrome as the mutation carriers, but lacking the familial mutation). We reviewed all pedigrees published between 1997 and 2009 with α‐synuclein, leucine‐rich repeat kinase 2, Parkin, or PTEN‐induced kinase 1 mutations with at least 2 affected individuals and known genetic status for the possible presence of phenocopies. Of 537 patients with clinical Parkinson's disease in 160 families meeting our inclusion criteria, 27 patients (5.0%) from 23 families (14.4%) were phenocopies. Phenocopies represented 3.8% of all blood relatives reported in the pedigrees containing phenocopies and an estimated 1.3% of all blood relatives in all pedigrees included. Both of these rates exceeded age‐specific prevalences of Parkinson's disease. In 4 families, the phenocopy was explained by another known mutation: In 2 pedigrees, a monogenic cause was likely; in another 2, secondary parkinsonism was suspected; and in the remaining 15 families, “sporadic Parkinson's disease” was suggested as the cause of disease in the phenocopy. The unexpectedly high number of phenocopies of mostly unknown origin within families with a seemingly known etiology of Parkinson's disease adds another level of complexity to genetic research of Parkinson's disease, as well as to the interpretation of genetic testing results in the clinical diagnostic setting. © 2011 Movement Disorder Society</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Christine Klein MD</name><affiliations><json:string>Morton and Gloria Shulman Movement Disorders Center and the Edmond J. 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Both of these rates exceeded age‐specific prevalences of Parkinson's disease. In 4 families, the phenocopy was explained by another known mutation: In 2 pedigrees, a monogenic cause was likely; in another 2, secondary parkinsonism was suspected; and in the remaining 15 families, “sporadic Parkinson's disease” was suggested as the cause of disease in the phenocopy. 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C.M. is a recipient of a new investigator award from the Canadian Institutes of Health Research. A.E.L. is supported, in part, from the Jack Clark Chair for Parkinson's Disease Research at the University of Toronto and the Edmond J. Safra Program in Parkinson's Disease at the University of Toronto and University Health Network.</note><note type="content">*Relevant conflicts of interest/financial disclosures: Nothing to report.</note><note type="content">*Full financial disclosures and author roles may be found in the online version of this article.</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">The curious case of phenocopies in families with genetic Parkinson's disease</title><author><persName><forename type="first">Christine</forename><surname>Klein</surname></persName><roleName type="degree">MD</roleName><note type="biography">Christine Klein, Rosalind Chuang, and Connie Marras contributed equally to this work.</note><affiliation>Christine Klein, Rosalind Chuang, and Connie Marras contributed equally to this work.</affiliation><affiliation>Morton and Gloria Shulman Movement Disorders Center and the Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada</affiliation><affiliation>Section of Clinical and Molecular Neurogenetics at the Department of Neurology, University of Lübeck, Lübeck, Germany</affiliation></author><author><persName><forename type="first">Rosalind</forename><surname>Chuang</surname></persName><roleName type="degree">MD</roleName><note type="biography">Christine Klein, Rosalind Chuang, and Connie Marras contributed equally to this work.</note><affiliation>Christine Klein, Rosalind Chuang, and Connie Marras contributed equally to this work.</affiliation><affiliation>Morton and Gloria Shulman Movement Disorders Center and the Edmond J. 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With reduced penetrance in dominant forms and manifesting heterozygotes in recessive forms of Parkinson's disease, it has been well recognized that inheritance patterns do not always follow classic Mendelian genetics. A novel twist to the puzzle is the presence of phenocopies (i.e., family members with the same clinical syndrome as the mutation carriers, but lacking the familial mutation). We reviewed all pedigrees published between 1997 and 2009 with α‐synuclein, leucine‐rich repeat kinase 2, Parkin, or PTEN‐induced kinase 1 mutations with at least 2 affected individuals and known genetic status for the possible presence of phenocopies. Of 537 patients with clinical Parkinson's disease in 160 families meeting our inclusion criteria, 27 patients (5.0%) from 23 families (14.4%) were phenocopies. Phenocopies represented 3.8% of all blood relatives reported in the pedigrees containing phenocopies and an estimated 1.3% of all blood relatives in all pedigrees included. Both of these rates exceeded age‐specific prevalences of Parkinson's disease. In 4 families, the phenocopy was explained by another known mutation: In 2 pedigrees, a monogenic cause was likely; in another 2, secondary parkinsonism was suspected; and in the remaining 15 families, “sporadic Parkinson's disease” was suggested as the cause of disease in the phenocopy. The unexpectedly high number of phenocopies of mostly unknown origin within families with a seemingly known etiology of Parkinson's disease adds another level of complexity to genetic research of Parkinson's disease, as well as to the interpretation of genetic testing results in the clinical diagnostic setting. © 2011 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>phenocopy</term></item><item><term>genetic testing</term></item><item><term>linkage analysis</term></item></list></keywords></textClass><textClass><keywords scheme="Journal Subject"><list><head>article category</head><item><term>Viewpoint</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2011-03-21">Received</change><change when="2011-05-26">Registration</change><change when="2011-08-15">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/10F7DC2554AD726CEEC38E30A5DF956F24D82293/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. 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Safra Program in Parkinson's Disease, Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada</unparsedAffiliation></affiliation><affiliation xml:id="af2" countryCode="DE" type="organization"><unparsedAffiliation>Section of Clinical and Molecular Neurogenetics at the Department of Neurology, University of Lübeck, Lübeck, Germany</unparsedAffiliation></affiliation></affiliationGroup><keywordGroup xml:lang="en" type="author"><keyword xml:id="kwd1">Parkinson's disease</keyword><keyword xml:id="kwd2">phenocopy</keyword><keyword xml:id="kwd3">genetic testing</keyword><keyword xml:id="kwd4">linkage analysis</keyword></keywordGroup><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><p>Monogenic forms of Parkinson's disease account for ∼3% of all “idiopathic” Parkinson's disease. With reduced penetrance in dominant forms and manifesting heterozygotes in recessive forms of Parkinson's disease, it has been well recognized that inheritance patterns do not always follow classic Mendelian genetics. A novel twist to the puzzle is the presence of phenocopies (i.e., family members with the same clinical syndrome as the mutation carriers, but lacking the familial mutation). We reviewed all pedigrees published between 1997 and 2009 with <i>α‐synuclein</i>, <i>leucine‐rich repeat kinase 2</i>, <i>Parkin</i>, or <i>PTEN‐induced kinase 1</i> mutations with at least 2 affected individuals and known genetic status for the possible presence of phenocopies. Of 537 patients with clinical Parkinson's disease in 160 families meeting our inclusion criteria, 27 patients (5.0%) from 23 families (14.4%) were phenocopies. Phenocopies represented 3.8% of all blood relatives reported in the pedigrees containing phenocopies and an estimated 1.3% of all blood relatives in all pedigrees included. Both of these rates exceeded age‐specific prevalences of Parkinson's disease. In 4 families, the phenocopy was explained by another known mutation: In 2 pedigrees, a monogenic cause was likely; in another 2, secondary parkinsonism was suspected; and in the remaining 15 families, “sporadic Parkinson's disease” was suggested as the cause of disease in the phenocopy. The unexpectedly high number of phenocopies of mostly unknown origin within families with a seemingly known etiology of Parkinson's disease adds another level of complexity to genetic research of Parkinson's disease, as well as to the interpretation of genetic testing results in the clinical diagnostic setting. © 2011 <i>Movement</i> Disorder Society</p></abstract></abstractGroup></contentMeta><noteGroup><note xml:id="fn1"><p><b>Funding agencies:</b> C.K. is the recipient of a career development award from the Volkswagen Foundation and from the Hermann and Lilly Schilling Foundation. C.M. is a recipient of a new investigator award from the Canadian Institutes of Health Research. A.E.L. is supported, in part, from the Jack Clark Chair for Parkinson's Disease Research at the University of Toronto and the Edmond J. Safra Program in Parkinson's Disease at the University of Toronto and University Health Network.</p></note><note xml:id="fn2"><p><b>Relevant conflicts of interest/financial disclosures:</b> Nothing to report.</p></note><note xml:id="fn3"><p>Full financial disclosures and author roles may be found in the online version of this article.</p></note><note xml:id="fn4"><p>Christine Klein, Rosalind Chuang, and Connie Marras contributed equally to this work.</p></note></noteGroup></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>The curious case of phenocopies in families with genetic Parkinson's disease</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>Phenocopies in Families with Genetic PD</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>The curious case of phenocopies in families with genetic Parkinson's disease</title></titleInfo><name type="personal"><namePart type="given">Christine</namePart><namePart type="family">Klein</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Morton and Gloria Shulman Movement Disorders Center and the Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada</affiliation><affiliation>Section of Clinical and Molecular Neurogenetics at the Department of Neurology, University of Lübeck, Lübeck, Germany</affiliation><description>Christine Klein, Rosalind Chuang, and Connie Marras contributed equally to this work.</description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Rosalind</namePart><namePart type="family">Chuang</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Morton and Gloria Shulman Movement Disorders Center and the Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada</affiliation><description>Christine Klein, Rosalind Chuang, and Connie Marras contributed equally to this work.</description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Connie</namePart><namePart type="family">Marras</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Morton and Gloria Shulman Movement Disorders Center and the Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Anthony E.</namePart><namePart type="family">Lang</namePart><namePart type="termsOfAddress">MD, FRCPC</namePart><affiliation>Morton and Gloria Shulman Movement Disorders Center and the Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada</affiliation><description>Correspondence: Toronto Western Hospital Morton and Gloria Shulman Movement Disorders Center, 399 Bathurst Street, Toronto M5T 2S8, Ontario, Canada</description><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">2011-08-15</dateIssued><dateCaptured encoding="w3cdtf">2011-03-21</dateCaptured><dateValid encoding="w3cdtf">2011-05-26</dateValid><copyrightDate encoding="w3cdtf">2011</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="tables">3</extent><extent unit="references">57</extent><extent unit="words">10390</extent></physicalDescription><abstract lang="en">Monogenic forms of Parkinson's disease account for ∼3% of all “idiopathic” Parkinson's disease. With reduced penetrance in dominant forms and manifesting heterozygotes in recessive forms of Parkinson's disease, it has been well recognized that inheritance patterns do not always follow classic Mendelian genetics. A novel twist to the puzzle is the presence of phenocopies (i.e., family members with the same clinical syndrome as the mutation carriers, but lacking the familial mutation). We reviewed all pedigrees published between 1997 and 2009 with α‐synuclein, leucine‐rich repeat kinase 2, Parkin, or PTEN‐induced kinase 1 mutations with at least 2 affected individuals and known genetic status for the possible presence of phenocopies. Of 537 patients with clinical Parkinson's disease in 160 families meeting our inclusion criteria, 27 patients (5.0%) from 23 families (14.4%) were phenocopies. Phenocopies represented 3.8% of all blood relatives reported in the pedigrees containing phenocopies and an estimated 1.3% of all blood relatives in all pedigrees included. Both of these rates exceeded age‐specific prevalences of Parkinson's disease. In 4 families, the phenocopy was explained by another known mutation: In 2 pedigrees, a monogenic cause was likely; in another 2, secondary parkinsonism was suspected; and in the remaining 15 families, “sporadic Parkinson's disease” was suggested as the cause of disease in the phenocopy. The unexpectedly high number of phenocopies of mostly unknown origin within families with a seemingly known etiology of Parkinson's disease adds another level of complexity to genetic research of Parkinson's disease, as well as to the interpretation of genetic testing results in the clinical diagnostic setting. © 2011 Movement Disorder Society</abstract><note type="content">*Funding agencies: C.K. is the recipient of a career development award from the Volkswagen Foundation and from the Hermann and Lilly Schilling Foundation. C.M. is a recipient of a new investigator award from the Canadian Institutes of Health Research. A.E.L. is supported, in part, from the Jack Clark Chair for Parkinson's Disease Research at the University of Toronto and the Edmond J. Safra Program in Parkinson's Disease at the University of Toronto and University Health Network.</note><note type="content">*Relevant conflicts of interest/financial disclosures: Nothing to report.</note><note type="content">*Full financial disclosures and author roles may be found in the online version of this article.</note><subject lang="en"><genre>Keywords</genre><topic>Parkinson's disease</topic><topic>phenocopy</topic><topic>genetic testing</topic><topic>linkage analysis</topic></subject><relatedItem type="host"><titleInfo><title>Movement Disorders</title></titleInfo><titleInfo type="abbreviated"><title>Mov. Disord.</title></titleInfo><genre type="Journal">journal</genre><subject><genre>article category</genre><topic>Viewpoint</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>2011</date><detail type="volume"><caption>vol.</caption><number>26</number></detail><detail type="issue"><caption>no.</caption><number>10</number></detail><extent unit="pages"><start>1793</start><end>1802</end><total>10</total></extent></part></relatedItem><identifier type="istex">10F7DC2554AD726CEEC38E30A5DF956F24D82293</identifier><identifier type="DOI">10.1002/mds.23853</identifier><identifier type="ArticleID">MDS23853</identifier><accessCondition type="use and reproduction" contentType="copyright">Copyright © 2011 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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