Reduced expression of the G209A α‐synuclein allele in familial parkinsonism
Identifieur interne : 001491 ( Main/Corpus ); précédent : 001490; suivant : 001492Reduced expression of the G209A α‐synuclein allele in familial parkinsonism
Auteurs : Katerina Markopoulou ; Zbigniew K. Wszolek ; Ronald F. Pfeiffer ; Bruce A. ChaseSource :
- Annals of Neurology [ 0364-5134 ] ; 1999-09.
Abstract
Missense mutations at the α‐synuclein gene have been associated with familial parkinsonism. We report that the phenotype of a kindred (Family H) with autosomal dominant, levodopa‐responsive parkinsonism maps to chromosomal region 4q21‐23 and that affected members of this kindred harbor a previously reported mutation (G209A) in exon 4 of the α‐synuclein gene. We assessed the expression of the G209A allele in lymphoblastoid cell lines established from 12 individuals heterozygous for the G209A allele. The expression of this allele is either absent or significantly reduced in 7 affected heterozygotes and in 3 asymptomatic heterozygotes who are older than the mean age at disease diagnosis for their generation. In contrast, it is expressed in 1 affected and 1 unaffected heterozygote. The unaffected heterozygote is younger than the mean age at disease diagnosis for their generation. The lack of or significantly reduced expression of the G209A allele in affected heterozygotes suggests that the timing of reduced expression may be critical for disease onset. If so, the parkinsonian phenotype may arise from haploinsufficiency at the α‐synuclein gene at a time point before symptom onset. In conclusion, reduced α‐synuclein gene expression may be important in the pathogenesis of parkinsonism.
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DOI: 10.1002/1531-8249(199909)46:3<374::AID-ANA13>3.0.CO;2-9
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We report that the phenotype of a kindred (Family H) with autosomal dominant, levodopa‐responsive parkinsonism maps to chromosomal region 4q21‐23 and that affected members of this kindred harbor a previously reported mutation (G209A) in exon 4 of the α‐synuclein gene. We assessed the expression of the G209A allele in lymphoblastoid cell lines established from 12 individuals heterozygous for the G209A allele. The expression of this allele is either absent or significantly reduced in 7 affected heterozygotes and in 3 asymptomatic heterozygotes who are older than the mean age at disease diagnosis for their generation. In contrast, it is expressed in 1 affected and 1 unaffected heterozygote. The unaffected heterozygote is younger than the mean age at disease diagnosis for their generation. The lack of or significantly reduced expression of the G209A allele in affected heterozygotes suggests that the timing of reduced expression may be critical for disease onset. If so, the parkinsonian phenotype may arise from haploinsufficiency at the α‐synuclein gene at a time point before symptom onset. In conclusion, reduced α‐synuclein gene expression may be important in the pathogenesis of parkinsonism.</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Katerina Markopoulou MD, PhD</name><affiliations><json:string>Department of Biology, University of Nebraska at Omaha, Omaha, NE</json:string><json:string>Section of Neurology, University of Nebraska Medical Center, Omaha, NE</json:string></affiliations></json:item><json:item><name>Zbigniew K. Wszolek MD</name><affiliations><json:string>Section of Neurology, University of Nebraska Medical Center, Omaha, NE</json:string></affiliations></json:item><json:item><name>Ronald F. Pfeiffer MD</name><affiliations><json:string>Department of Neurology, University of Tennessee, Memphis, TN</json:string></affiliations></json:item><json:item><name>Bruce A. 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In contrast, it is expressed in 1 affected and 1 unaffected heterozygote. The unaffected heterozygote is younger than the mean age at disease diagnosis for their generation. The lack of or significantly reduced expression of the G209A allele in affected heterozygotes suggests that the timing of reduced expression may be critical for disease onset. If so, the parkinsonian phenotype may arise from haploinsufficiency at the α‐synuclein gene at a time point before symptom onset. 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If so, the parkinsonian phenotype may arise from haploinsufficiency at the α‐synuclein gene at a time point before symptom onset. 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Expression</title></titleGroup><creators><creator xml:id="au1" creatorRole="author" affiliationRef="#af1 #af2" corresponding="yes"><personName><givenNames>Katerina</givenNames><familyName>Markopoulou</familyName><degrees>MD, PhD</degrees></personName></creator><creator xml:id="au2" creatorRole="author" affiliationRef="#af2"><personName><givenNames>Zbigniew K.</givenNames><familyName>Wszolek</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au3" creatorRole="author" affiliationRef="#af3"><personName><givenNames>Ronald F.</givenNames><familyName>Pfeiffer</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au4" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Bruce A.</givenNames><familyName>Chase</familyName><degrees>PhD</degrees></personName></creator></creators><affiliationGroup><affiliation xml:id="af1" countryCode="US" type="organization"><unparsedAffiliation>Department of Biology, University of Nebraska at Omaha, Omaha, NE</unparsedAffiliation></affiliation><affiliation xml:id="af2" countryCode="US" type="organization"><unparsedAffiliation>Section of Neurology, University of Nebraska Medical Center, Omaha, NE</unparsedAffiliation></affiliation><affiliation xml:id="af3" countryCode="US" type="organization"><unparsedAffiliation>Department of Neurology, University of Tennessee, Memphis, TN</unparsedAffiliation></affiliation></affiliationGroup><fundingInfo><fundingAgency>Parkinson's Disease Foundation</fundingAgency></fundingInfo><fundingInfo><fundingAgency>National Parkinson Foundation</fundingAgency></fundingInfo><fundingInfo><fundingAgency>University Committee on Research at the University of Nebraska at Omaha</fundingAgency></fundingInfo><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><p>Missense mutations at the α‐synuclein gene have been associated with familial parkinsonism. We report that the phenotype of a kindred (Family H) with autosomal dominant, levodopa‐responsive parkinsonism maps to chromosomal region 4q21‐23 and that affected members of this kindred harbor a previously reported mutation (G209A) in exon 4 of the α‐synuclein gene. We assessed the expression of the G209A allele in lymphoblastoid cell lines established from 12 individuals heterozygous for the G209A allele. The expression of this allele is either absent or significantly reduced in 7 affected heterozygotes and in 3 asymptomatic heterozygotes who are older than the mean age at disease diagnosis for their generation. In contrast, it is expressed in 1 affected and 1 unaffected heterozygote. The unaffected heterozygote is younger than the mean age at disease diagnosis for their generation. The lack of or significantly reduced expression of the G209A allele in affected heterozygotes suggests that the timing of reduced expression may be critical for disease onset. If so, the parkinsonian phenotype may arise from haploinsufficiency at the α‐synuclein gene at a time point before symptom onset. In conclusion, reduced α‐synuclein gene expression may be important in the pathogenesis of parkinsonism.</p></abstract></abstractGroup></contentMeta></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Reduced expression of the G209A α‐synuclein allele in familial parkinsonism</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>Reduced G209A α‐Synuclein Expression</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Reduced expression of the G209A α‐synuclein allele in familial parkinsonism</title></titleInfo><name type="personal"><namePart type="given">Katerina</namePart><namePart type="family">Markopoulou</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Department of Biology, University of Nebraska at Omaha, Omaha, NE</affiliation><affiliation>Section of Neurology, University of Nebraska Medical Center, Omaha, NE</affiliation><description>Correspondence: Section of Neurology, University of Nebraska Medical Center, 600 S. 42nd Street, Omaha, NE 68198‐2045</description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Zbigniew K.</namePart><namePart type="family">Wszolek</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Section of Neurology, University of Nebraska Medical Center, Omaha, NE</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Ronald F.</namePart><namePart type="family">Pfeiffer</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neurology, University of Tennessee, Memphis, TN</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Bruce A.</namePart><namePart type="family">Chase</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Department of Biology, University of Nebraska at Omaha, Omaha, NE</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="article" displayLabel="article"></genre><originInfo><publisher>John Wiley & Sons, Inc.</publisher><place><placeTerm type="text">New York</placeTerm></place><dateIssued encoding="w3cdtf">1999-09</dateIssued><dateCaptured encoding="w3cdtf">1998-11-18</dateCaptured><dateValid encoding="w3cdtf">1999-04-23</dateValid><copyrightDate encoding="w3cdtf">1999</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">4</extent><extent unit="tables">2</extent><extent unit="references">47</extent><extent unit="words">5286</extent></physicalDescription><abstract lang="en">Missense mutations at the α‐synuclein gene have been associated with familial parkinsonism. We report that the phenotype of a kindred (Family H) with autosomal dominant, levodopa‐responsive parkinsonism maps to chromosomal region 4q21‐23 and that affected members of this kindred harbor a previously reported mutation (G209A) in exon 4 of the α‐synuclein gene. We assessed the expression of the G209A allele in lymphoblastoid cell lines established from 12 individuals heterozygous for the G209A allele. The expression of this allele is either absent or significantly reduced in 7 affected heterozygotes and in 3 asymptomatic heterozygotes who are older than the mean age at disease diagnosis for their generation. In contrast, it is expressed in 1 affected and 1 unaffected heterozygote. The unaffected heterozygote is younger than the mean age at disease diagnosis for their generation. The lack of or significantly reduced expression of the G209A allele in affected heterozygotes suggests that the timing of reduced expression may be critical for disease onset. If so, the parkinsonian phenotype may arise from haploinsufficiency at the α‐synuclein gene at a time point before symptom onset. In conclusion, reduced α‐synuclein gene expression may be important in the pathogenesis of parkinsonism.</abstract><note type="funding">Parkinson's Disease Foundation</note><note type="funding">National Parkinson Foundation</note><note type="funding">University Committee on Research at the University of Nebraska at Omaha</note><relatedItem type="host"><titleInfo><title>Annals of Neurology</title><subTitle>Official Journal of the American Neurological Association and the Child Neurology Society</subTitle></titleInfo><titleInfo type="abbreviated"><title>Ann Neurol.</title></titleInfo><genre type="Journal">journal</genre><subject><genre>article category</genre><topic>Original Article</topic></subject><identifier type="ISSN">0364-5134</identifier><identifier type="eISSN">1531-8249</identifier><identifier type="DOI">10.1002/(ISSN)1531-8249</identifier><identifier type="PublisherID">ANA</identifier><part><date>1999</date><detail type="volume"><caption>vol.</caption><number>46</number></detail><detail type="issue"><caption>no.</caption><number>3</number></detail><extent unit="pages"><start>374</start><end>381</end><total>8</total></extent></part></relatedItem><identifier type="istex">A14FE4AB55A3642D28F2D1286349E074E907B48A</identifier><identifier type="DOI">10.1002/1531-8249(199909)46:3<374::AID-ANA13>3.0.CO;2-9</identifier><identifier type="ArticleID">ANA13</identifier><accessCondition type="use and reproduction" contentType="copyright">Copyright © 1999 American Neurological Association</accessCondition><recordInfo><recordContentSource>WILEY</recordContentSource><recordOrigin>John Wiley & Sons, Inc.</recordOrigin></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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|flux= Main
|étape= Corpus
|type= RBID
|clé= ISTEX:A14FE4AB55A3642D28F2D1286349E074E907B48A
|texte= Reduced expression of the G209A α‐synuclein allele in familial parkinsonism
}}
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