Suggestive linkage to chromosome 19 in a large Cuban family with late‐onset Parkinson's disease
Identifieur interne : 000483 ( Istex/Corpus ); précédent : 000482; suivant : 000484Suggestive linkage to chromosome 19 in a large Cuban family with late‐onset Parkinson's disease
Auteurs : Aida M. Bertoli-Avella ; Jose L. Giroud-Benitez ; Vincenzo Bonifati ; Eduardo Alvarez-Gonzalez ; Luis Heredero-Baute ; Cornelia M. Van Duijn ; Peter HeutinkSource :
- Movement Disorders [ 0885-3185 ] ; 2003-11.
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Abstract
The identification of disease genes using family‐based approaches has provided important insights into the pathogenesis of Parkinson's disease (PD) demonstrating the importance of genetic studies on monogenic forms of the disease. We studied a large Cuban family with typical, late‐onset PD and probable autosomal dominant inheritance. Mean age at onset was 61.2 years (±12.53, 45–76). Other phenotypes such as essential tremor and atypical parkinsonism were observed in this family. We carried out a genome‐wide scan and linkage analyses. The genetic data were analyzed using a conservative model in which only patients with clinically definite or likely PD were considered affected, other phenotypes were regarded as “unknown.” Multipoint analyses yielded a maximum LOD of 2.26 between markers D19S221 and D19S840. Haplotype analysis showed a region on chromosome 19 shared by six of seven PD patients. The essential tremor phenotype and the atypical parkinsonism do not segregate with this haplotype, suggesting a different etiology. Our findings suggest the presence of a novel locus for PD on chromosome 19p13.3–q12. We propose that an oligogenic model with moderate contribution of two or three genes rather than a “pure” monogenic model might explain better the wide range in age at onset, the reduced penetrance and the phenotypical variability observed in PD families. © 2003 Movement Disorder Society
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DOI: 10.1002/mds.10534
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ISTEX:9FF88431CFE37F10661006F5D08FA77501381965Le document en format XML
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We studied a large Cuban family with typical, late‐onset PD and probable autosomal dominant inheritance. Mean age at onset was 61.2 years (±12.53, 45–76). Other phenotypes such as essential tremor and atypical parkinsonism were observed in this family. We carried out a genome‐wide scan and linkage analyses. The genetic data were analyzed using a conservative model in which only patients with clinically definite or likely PD were considered affected, other phenotypes were regarded as “unknown.” Multipoint analyses yielded a maximum LOD of 2.26 between markers D19S221 and D19S840. Haplotype analysis showed a region on chromosome 19 shared by six of seven PD patients. The essential tremor phenotype and the atypical parkinsonism do not segregate with this haplotype, suggesting a different etiology. Our findings suggest the presence of a novel locus for PD on chromosome 19p13.3–q12. We propose that an oligogenic model with moderate contribution of two or three genes rather than a “pure” monogenic model might explain better the wide range in age at onset, the reduced penetrance and the phenotypical variability observed in PD families. © 2003 Movement Disorder Society</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Aida M. Bertoli‐Avella MD</name><affiliations><json:string>Department of Epidemiology and Biostatistics, Erasmus Medical Center, Rotterdam, The Netherlands</json:string><json:string>National Center of Medical Genetics, Higher Institute of Medical Sciences, Havana, Cuba</json:string><json:string>Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands</json:string></affiliations></json:item><json:item><name>Jose L. Giroud‐Benitez MD</name><affiliations><json:string>University Hospital “Carlos J. 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Van Duijn PhD</name><affiliations><json:string>Department of Epidemiology and Biostatistics, Erasmus Medical Center, Rotterdam, The Netherlands</json:string></affiliations></json:item><json:item><name>Peter Heutink PhD</name><affiliations><json:string>Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands</json:string><json:string>Current Address: Section Medical Genomics, Department of Clinical Genetics and Human Genetics, VU Medical Center, Amsterdam, The Netherlands</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>late‐onset</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>autosomal dominant</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>genetic linkage</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>genome scan</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>chromosome 19p13.3–q12</value></json:item></subject><language><json:string>eng</json:string></language><abstract>The identification of disease genes using family‐based approaches has provided important insights into the pathogenesis of Parkinson's disease (PD) demonstrating the importance of genetic studies on monogenic forms of the disease. We studied a large Cuban family with typical, late‐onset PD and probable autosomal dominant inheritance. Mean age at onset was 61.2 years (±12.53, 45–76). Other phenotypes such as essential tremor and atypical parkinsonism were observed in this family. We carried out a genome‐wide scan and linkage analyses. The genetic data were analyzed using a conservative model in which only patients with clinically definite or likely PD were considered affected, other phenotypes were regarded as “unknown.” Multipoint analyses yielded a maximum LOD of 2.26 between markers D19S221 and D19S840. Haplotype analysis showed a region on chromosome 19 shared by six of seven PD patients. The essential tremor phenotype and the atypical parkinsonism do not segregate with this haplotype, suggesting a different etiology. Our findings suggest the presence of a novel locus for PD on chromosome 19p13.3–q12. 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Finlay,” Havana, Cuba</affiliation></author><author><persName><forename type="first">Vincenzo</forename><surname>Bonifati</surname><roleName type="degree">MD</roleName></persName><affiliation>Department of Neurological Sciences, University La Sapienza, Rome, Italy</affiliation><affiliation>Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands</affiliation></author><author><persName><forename type="first">Eduardo</forename><surname>Alvarez‐Gonzalez</surname><roleName type="degree">MD</roleName></persName><affiliation>International Neurological Restoration Center, Havana, Cuba</affiliation></author><author><persName><forename type="first">Luis</forename><surname>Heredero‐Baute</surname><roleName type="degree">MD, PhD</roleName></persName><affiliation>National Center of Medical Genetics, Higher Institute of Medical Sciences, Havana, Cuba</affiliation></author><author><persName><forename type="first">Cornelia M.</forename><surname>Van Duijn</surname><roleName type="degree">PhD</roleName></persName><affiliation>Department of Epidemiology and Biostatistics, Erasmus Medical Center, Rotterdam, The Netherlands</affiliation></author><author><persName><forename type="first">Peter</forename><surname>Heutink</surname><roleName type="degree">PhD</roleName></persName><affiliation>Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands</affiliation><affiliation>Current Address: Section Medical Genomics, Department of Clinical Genetics and Human Genetics, VU Medical Center, Amsterdam, The Netherlands</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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We propose that an oligogenic model with moderate contribution of two or three genes rather than a “pure” monogenic model might explain better the wide range in age at onset, the reduced penetrance and the phenotypical variability observed in PD families. © 2003 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>late‐onset</term></item><item><term>autosomal dominant</term></item><item><term>genetic linkage</term></item><item><term>genome scan</term></item><item><term>chromosome 19p13.3–q12</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="2003-01-30">Received</change><change when="2003-05-28">Registration</change><change when="2003-11">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/9FF88431CFE37F10661006F5D08FA77501381965/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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Finlay,” Havana, Cuba</unparsedAffiliation></affiliation><affiliation xml:id="af4" countryCode="IT" type="organization"><unparsedAffiliation>Department of Neurological Sciences, University La Sapienza, Rome, Italy</unparsedAffiliation></affiliation><affiliation xml:id="af5" countryCode="CU" type="organization"><unparsedAffiliation>International Neurological Restoration Center, Havana, Cuba</unparsedAffiliation></affiliation><affiliation xml:id="af6" countryCode="NL" type="organization"><unparsedAffiliation>Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands</unparsedAffiliation></affiliation><affiliation xml:id="curr1" countryCode="NL"><unparsedAffiliation>Section Medical Genomics, Department of Clinical Genetics and Human Genetics, VU Medical Center, Amsterdam, The Netherlands</unparsedAffiliation></affiliation></affiliationGroup><keywordGroup xml:lang="en" type="author"><keyword xml:id="kwd1">Parkinson's disease</keyword><keyword xml:id="kwd2">late‐onset</keyword><keyword xml:id="kwd3">autosomal dominant</keyword><keyword xml:id="kwd4">genetic linkage</keyword><keyword xml:id="kwd5">genome scan</keyword><keyword xml:id="kwd6">chromosome 19p13.3–q12</keyword></keywordGroup><fundingInfo><fundingAgency>Princes Beatrix Foundation</fundingAgency></fundingInfo><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><p>The identification of disease genes using family‐based approaches has provided important insights into the pathogenesis of Parkinson's disease (PD) demonstrating the importance of genetic studies on monogenic forms of the disease. We studied a large Cuban family with typical, late‐onset PD and probable autosomal dominant inheritance. Mean age at onset was 61.2 years (±12.53, 45–76). Other phenotypes such as essential tremor and atypical parkinsonism were observed in this family. We carried out a genome‐wide scan and linkage analyses. The genetic data were analyzed using a conservative model in which only patients with clinically definite or likely PD were considered affected, other phenotypes were regarded as “unknown.” Multipoint analyses yielded a maximum LOD of 2.26 between markers D19S221 and D19S840. Haplotype analysis showed a region on chromosome 19 shared by six of seven PD patients. The essential tremor phenotype and the atypical parkinsonism do not segregate with this haplotype, suggesting a different etiology. Our findings suggest the presence of a novel locus for PD on chromosome 19p13.3–q12. We propose that an oligogenic model with moderate contribution of two or three genes rather than a “pure” monogenic model might explain better the wide range in age at onset, the reduced penetrance and the phenotypical variability observed in PD families. © 2003 Movement Disorder Society</p></abstract></abstractGroup></contentMeta></header></component></istex:document></istex:metadataXml><!--Version 0.6 générée le 3-12-2015--><mods version="3.6"><titleInfo lang="en"><title>Suggestive linkage to chromosome 19 in a large Cuban family with late‐onset Parkinson's disease</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>Chromosome 19 Haplotype in a Family with PD</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Suggestive linkage to chromosome 19 in a large Cuban family with late‐onset Parkinson's disease</title></titleInfo><name type="personal"><namePart type="given">Aida M.</namePart><namePart type="family">Bertoli‐Avella</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Epidemiology and Biostatistics, Erasmus Medical Center, Rotterdam, The Netherlands</affiliation><affiliation>National Center of Medical Genetics, Higher Institute of Medical Sciences, Havana, Cuba</affiliation><affiliation>Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands</affiliation><description>Correspondence: Genetic Epidemiology Unit, Department of Epidemiology & Biostatistics, Erasmus Medical Center, PO Box 1738, 3000 DR Rotterdam, The Netherlands</description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jose L.</namePart><namePart type="family">Giroud‐Benitez</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>University Hospital “Carlos J. Finlay,” Havana, Cuba</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Vincenzo</namePart><namePart type="family">Bonifati</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neurological Sciences, University La Sapienza, Rome, Italy</affiliation><affiliation>Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Eduardo</namePart><namePart type="family">Alvarez‐Gonzalez</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>International Neurological Restoration Center, Havana, Cuba</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Luis</namePart><namePart type="family">Heredero‐Baute</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>National Center of Medical Genetics, Higher Institute of Medical Sciences, Havana, Cuba</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Cornelia M.</namePart><namePart type="family">Van Duijn</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Department of Epidemiology and Biostatistics, Erasmus Medical Center, Rotterdam, The Netherlands</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Peter</namePart><namePart type="family">Heutink</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands</affiliation><affiliation>Current Address: Section Medical Genomics, Department of Clinical Genetics and Human Genetics, VU Medical Center, Amsterdam, The Netherlands</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">2003-11</dateIssued><dateCaptured encoding="w3cdtf">2003-01-30</dateCaptured><dateValid encoding="w3cdtf">2003-05-28</dateValid><copyrightDate encoding="w3cdtf">2003</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">3</extent><extent unit="tables">3</extent><extent unit="references">51</extent><extent unit="words">6093</extent></physicalDescription><abstract lang="en">The identification of disease genes using family‐based approaches has provided important insights into the pathogenesis of Parkinson's disease (PD) demonstrating the importance of genetic studies on monogenic forms of the disease. We studied a large Cuban family with typical, late‐onset PD and probable autosomal dominant inheritance. Mean age at onset was 61.2 years (±12.53, 45–76). Other phenotypes such as essential tremor and atypical parkinsonism were observed in this family. We carried out a genome‐wide scan and linkage analyses. The genetic data were analyzed using a conservative model in which only patients with clinically definite or likely PD were considered affected, other phenotypes were regarded as “unknown.” Multipoint analyses yielded a maximum LOD of 2.26 between markers D19S221 and D19S840. Haplotype analysis showed a region on chromosome 19 shared by six of seven PD patients. The essential tremor phenotype and the atypical parkinsonism do not segregate with this haplotype, suggesting a different etiology. Our findings suggest the presence of a novel locus for PD on chromosome 19p13.3–q12. We propose that an oligogenic model with moderate contribution of two or three genes rather than a “pure” monogenic model might explain better the wide range in age at onset, the reduced penetrance and the phenotypical variability observed in PD families. © 2003 Movement Disorder Society</abstract><note type="funding">Princes Beatrix Foundation</note><subject lang="en"><genre>Keywords</genre><topic>Parkinson's disease</topic><topic>late‐onset</topic><topic>autosomal dominant</topic><topic>genetic linkage</topic><topic>genome scan</topic><topic>chromosome 19p13.3–q12</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. 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