Parkin deletions in a family with adult‐onset, tremor‐dominant parkinsonism: Expanding the phenotype
Identifieur interne : 002563 ( Main/Corpus ); précédent : 002562; suivant : 002564Parkin deletions in a family with adult‐onset, tremor‐dominant parkinsonism: Expanding the phenotype
Auteurs : Christine Klein ; Peter P. Pramstaller ; Bernhard Kis ; Curtis C. Page ; Martin Kann ; Joanne Leung ; Heather Woodward ; Claudio C. Castellan ; Monika Scherer ; Peter Vieregge ; Xandra O. Breakefield ; Patricia L. Kramer ; Laurie J. OzeliusSource :
- Annals of Neurology [ 0364-5134 ] ; 2000-07.
Abstract
A gene for autosomal recessive parkinsonism, PARK2 (parkin), has recently been identified on chromosome 6q and shown to be mutated in Japanese and European families, mostly with early‐onset parkinsonism. Here we present a large pedigree from South Tyrol (a region of northern Italy) with adult‐onset, clinically typical tremor‐dominant parkinsonism of apparently autosomal dominant inheritance. Haplotype analysis excluded linkage to the chromosome 2p, 4p, and 4q regions that harbor genes associated with autosomal dominant parkinsonism, but implicated the parkin locus on chromosome 6q. Compound heterozygous deletions in the parkin gene (one large and one truncating) were identified in 4 affected male siblings. The patients were clinically indistinguishable from most patients with idiopathic Parkinson's disease. None of them displayed any of the clinical hallmarks described in patients with previously reported parkin mutations, including diurnal fluctuations, benefit from sleep, foot dystonia, hyperreflexia, and early susceptibility to levodopa‐induced dyskinesias. Two affected female individuals carried one (truncating) of the two deletions in a heterozygous state with an apparently normal allele. We conclude that the phenotypic spectrum associated with mutations in the parkin gene is broader than previously reported, suggesting that this gene may be important in the etiology of the more frequent late‐onset typical Parkinson's disease. Ann Neurol 2000;48:65–71
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DOI: 10.1002/1531-8249(200007)48:1<65::AID-ANA10>3.0.CO;2-L
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Pramstaller</name><affiliation><mods:affiliation>Department of Neurology, Regional General Hospital, Bolzano‐Bozen, Italy</mods:affiliation></affiliation></author><author><name sortKey="Kis, Bernhard" sort="Kis, Bernhard" uniqKey="Kis B" first="Bernhard" last="Kis">Bernhard Kis</name><affiliation><mods:affiliation>Department of Neurology, Medical University of Lübeck, Lübeck, Germany</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Neurology, Regional General Hospital, Bolzano‐Bozen, Italy</mods:affiliation></affiliation></author><author><name sortKey="Page, Curtis C" sort="Page, Curtis C" uniqKey="Page C" first="Curtis C." last="Page">Curtis C. 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Castellan</name><affiliation><mods:affiliation>Department of Genetics, Regional General Hospital, Bolzano‐Bozen, Italy</mods:affiliation></affiliation></author><author><name sortKey="Scherer, Monika" sort="Scherer, Monika" uniqKey="Scherer M" first="Monika" last="Scherer">Monika Scherer</name><affiliation><mods:affiliation>Department of Neurology, Regional General Hospital, Bolzano‐Bozen, Italy</mods:affiliation></affiliation></author><author><name sortKey="Vieregge, Peter" sort="Vieregge, Peter" uniqKey="Vieregge P" first="Peter" last="Vieregge">Peter Vieregge</name><affiliation><mods:affiliation>Department of Neurology, Medical University of Lübeck, Lübeck, Germany</mods:affiliation></affiliation></author><author><name sortKey="Breakefield, Xandra O" sort="Breakefield, Xandra O" uniqKey="Breakefield X" first="Xandra O." last="Breakefield">Xandra O. Breakefield</name><affiliation><mods:affiliation>Molecular Neurogenetics Unit, Massachusetts General Hospital Departments of Neurology and Genetics and Neuroscience Program, Harvard Medical School, Boston, MA</mods:affiliation></affiliation></author><author><name sortKey="Kramer, Patricia L" sort="Kramer, Patricia L" uniqKey="Kramer P" first="Patricia L." last="Kramer">Patricia L. Kramer</name><affiliation><mods:affiliation>Department of Neurology, Oregon Health Science University, Portland, OR</mods:affiliation></affiliation></author><author><name sortKey="Ozelius, Laurie J" sort="Ozelius, Laurie J" uniqKey="Ozelius L" first="Laurie J." last="Ozelius">Laurie J. Ozelius</name><affiliation><mods:affiliation>Molecular Neurogenetics Unit, Massachusetts General Hospital Departments of Neurology and Genetics and Neuroscience Program, Harvard Medical School, Boston, MA</mods:affiliation></affiliation><affiliation><mods:affiliation>Molecular Genetics, Albert Einstein College of Medicine, Bronx, NY</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Annals of Neurology</title><title level="j" type="abbrev">Ann Neurol.</title><idno type="ISSN">0364-5134</idno><idno type="eISSN">1531-8249</idno><imprint><publisher>John Wiley & Sons, Inc.</publisher><pubPlace>New York</pubPlace><date type="published" when="2000-07">2000-07</date><biblScope unit="volume">48</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="65">65</biblScope><biblScope unit="page" to="71">71</biblScope></imprint><idno type="ISSN">0364-5134</idno></series><idno type="istex">D02851CDA583E83DBB672D80151865CEC67EFA55</idno><idno type="DOI">10.1002/1531-8249(200007)48:1<65::AID-ANA10>3.0.CO;2-L</idno><idno type="ArticleID">ANA10</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0364-5134</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">A gene for autosomal recessive parkinsonism, PARK2 (parkin), has recently been identified on chromosome 6q and shown to be mutated in Japanese and European families, mostly with early‐onset parkinsonism. Here we present a large pedigree from South Tyrol (a region of northern Italy) with adult‐onset, clinically typical tremor‐dominant parkinsonism of apparently autosomal dominant inheritance. Haplotype analysis excluded linkage to the chromosome 2p, 4p, and 4q regions that harbor genes associated with autosomal dominant parkinsonism, but implicated the parkin locus on chromosome 6q. Compound heterozygous deletions in the parkin gene (one large and one truncating) were identified in 4 affected male siblings. The patients were clinically indistinguishable from most patients with idiopathic Parkinson's disease. None of them displayed any of the clinical hallmarks described in patients with previously reported parkin mutations, including diurnal fluctuations, benefit from sleep, foot dystonia, hyperreflexia, and early susceptibility to levodopa‐induced dyskinesias. Two affected female individuals carried one (truncating) of the two deletions in a heterozygous state with an apparently normal allele. We conclude that the phenotypic spectrum associated with mutations in the parkin gene is broader than previously reported, suggesting that this gene may be important in the etiology of the more frequent late‐onset typical Parkinson's disease. Ann Neurol 2000;48:65–71</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Christine Klein MD</name><affiliations><json:string>Molecular Neurogenetics Unit, Massachusetts General Hospital Departments of Neurology and Genetics and Neuroscience Program, Harvard Medical School, Boston, MA</json:string><json:string>Department of Neurology, Medical University of Lübeck, Lübeck, Germany</json:string></affiliations></json:item><json:item><name>Peter P. Pramstaller MD</name><affiliations><json:string>Department of Neurology, Regional General Hospital, Bolzano‐Bozen, Italy</json:string></affiliations></json:item><json:item><name>Bernhard Kis MD</name><affiliations><json:string>Department of Neurology, Medical University of Lübeck, Lübeck, Germany</json:string><json:string>Department of Neurology, Regional General Hospital, Bolzano‐Bozen, Italy</json:string></affiliations></json:item><json:item><name>Curtis C. Page BA</name><affiliations><json:string>Molecular Neurogenetics Unit, Massachusetts General Hospital Departments of Neurology and Genetics and Neuroscience Program, Harvard Medical School, Boston, MA</json:string></affiliations></json:item><json:item><name>Martin Kann BS</name><affiliations><json:string>Molecular Neurogenetics Unit, Massachusetts General Hospital Departments of Neurology and Genetics and Neuroscience Program, Harvard Medical School, Boston, MA</json:string></affiliations></json:item><json:item><name>Joanne Leung BS</name><affiliations><json:string>Molecular Neurogenetics Unit, Massachusetts General Hospital Departments of Neurology and Genetics and Neuroscience Program, Harvard Medical School, Boston, MA</json:string></affiliations></json:item><json:item><name>Heather Woodward BS</name><affiliations><json:string>Molecular Neurogenetics Unit, Massachusetts General Hospital Departments of Neurology and Genetics and Neuroscience Program, Harvard Medical School, Boston, MA</json:string></affiliations></json:item><json:item><name>Claudio C. Castellan MD</name><affiliations><json:string>Department of Genetics, Regional General Hospital, Bolzano‐Bozen, Italy</json:string></affiliations></json:item><json:item><name>Monika Scherer MD</name><affiliations><json:string>Department of Neurology, Regional General Hospital, Bolzano‐Bozen, Italy</json:string></affiliations></json:item><json:item><name>Peter Vieregge MD</name><affiliations><json:string>Department of Neurology, Medical University of Lübeck, Lübeck, Germany</json:string></affiliations></json:item><json:item><name>Xandra O. Breakefield PhD</name><affiliations><json:string>Molecular Neurogenetics Unit, Massachusetts General Hospital Departments of Neurology and Genetics and Neuroscience Program, Harvard Medical School, Boston, MA</json:string></affiliations></json:item><json:item><name>Patricia L. Kramer PhD</name><affiliations><json:string>Department of Neurology, Oregon Health Science University, Portland, OR</json:string></affiliations></json:item><json:item><name>Laurie J. Ozelius PhD</name><affiliations><json:string>Molecular Neurogenetics Unit, Massachusetts General Hospital Departments of Neurology and Genetics and Neuroscience Program, Harvard Medical School, Boston, MA</json:string><json:string>Molecular Genetics, Albert Einstein College of Medicine, Bronx, NY</json:string></affiliations></json:item></author><articleId><json:string>ANA10</json:string></articleId><language><json:string>eng</json:string></language><abstract>A gene for autosomal recessive parkinsonism, PARK2 (parkin), has recently been identified on chromosome 6q and shown to be mutated in Japanese and European families, mostly with early‐onset parkinsonism. Here we present a large pedigree from South Tyrol (a region of northern Italy) with adult‐onset, clinically typical tremor‐dominant parkinsonism of apparently autosomal dominant inheritance. Haplotype analysis excluded linkage to the chromosome 2p, 4p, and 4q regions that harbor genes associated with autosomal dominant parkinsonism, but implicated the parkin locus on chromosome 6q. Compound heterozygous deletions in the parkin gene (one large and one truncating) were identified in 4 affected male siblings. The patients were clinically indistinguishable from most patients with idiopathic Parkinson's disease. None of them displayed any of the clinical hallmarks described in patients with previously reported parkin mutations, including diurnal fluctuations, benefit from sleep, foot dystonia, hyperreflexia, and early susceptibility to levodopa‐induced dyskinesias. Two affected female individuals carried one (truncating) of the two deletions in a heterozygous state with an apparently normal allele. We conclude that the phenotypic spectrum associated with mutations in the parkin gene is broader than previously reported, suggesting that this gene may be important in the etiology of the more frequent late‐onset typical Parkinson's disease. 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type="first">Christine</forename><surname>Klein</surname></persName><roleName type="degree">MD</roleName><affiliation>Molecular Neurogenetics Unit, Massachusetts General Hospital Departments of Neurology and Genetics and Neuroscience Program, Harvard Medical School, Boston, MA</affiliation><affiliation>Department of Neurology, Medical University of Lübeck, Lübeck, Germany</affiliation></author><author><persName><forename type="first">Peter P.</forename><surname>Pramstaller</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Neurology, Regional General Hospital, Bolzano‐Bozen, Italy</affiliation></author><author><persName><forename type="first">Bernhard</forename><surname>Kis</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Neurology, Medical University of Lübeck, Lübeck, Germany</affiliation><affiliation>Department of Neurology, Regional General Hospital, Bolzano‐Bozen, Italy</affiliation></author><author><persName><forename type="first">Curtis C.</forename><surname>Page</surname></persName><roleName type="degree">BA</roleName><affiliation>Molecular Neurogenetics Unit, Massachusetts General Hospital Departments of Neurology and Genetics and Neuroscience Program, Harvard Medical School, Boston, MA</affiliation></author><author><persName><forename type="first">Martin</forename><surname>Kann</surname></persName><roleName type="degree">BS</roleName><affiliation>Molecular Neurogenetics Unit, Massachusetts General Hospital Departments of Neurology and Genetics and Neuroscience Program, Harvard Medical School, Boston, MA</affiliation></author><author><persName><forename type="first">Joanne</forename><surname>Leung</surname></persName><roleName type="degree">BS</roleName><affiliation>Molecular Neurogenetics Unit, Massachusetts General Hospital Departments of Neurology and Genetics and Neuroscience Program, Harvard Medical School, Boston, MA</affiliation></author><author><persName><forename type="first">Heather</forename><surname>Woodward</surname></persName><roleName type="degree">BS</roleName><affiliation>Molecular Neurogenetics Unit, Massachusetts General Hospital Departments of Neurology and Genetics and Neuroscience Program, Harvard Medical School, Boston, MA</affiliation></author><author><persName><forename type="first">Claudio C.</forename><surname>Castellan</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Genetics, Regional General Hospital, Bolzano‐Bozen, Italy</affiliation></author><author><persName><forename type="first">Monika</forename><surname>Scherer</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Neurology, Regional General Hospital, Bolzano‐Bozen, Italy</affiliation></author><author><persName><forename type="first">Peter</forename><surname>Vieregge</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Neurology, Medical University of Lübeck, Lübeck, Germany</affiliation></author><author><persName><forename type="first">Xandra O.</forename><surname>Breakefield</surname></persName><roleName type="degree">PhD</roleName><affiliation>Molecular Neurogenetics Unit, Massachusetts General Hospital Departments of Neurology and Genetics and Neuroscience Program, Harvard Medical School, Boston, MA</affiliation></author><author><persName><forename type="first">Patricia L.</forename><surname>Kramer</surname></persName><roleName type="degree">PhD</roleName><affiliation>Department of Neurology, Oregon Health Science University, Portland, OR</affiliation></author><author><persName><forename type="first">Laurie J.</forename><surname>Ozelius</surname></persName><roleName type="degree">PhD</roleName><note type="correspondence"><p>Correspondence: Molecular Genetics, AECOM, 1300 Morris Park Avenue, Bronx, NY 10461</p></note><affiliation>Molecular Neurogenetics Unit, Massachusetts General Hospital Departments of Neurology and Genetics and Neuroscience Program, Harvard Medical School, Boston, MA</affiliation><affiliation>Molecular Genetics, Albert Einstein College of Medicine, Bronx, NY</affiliation></author></analytic><monogr><title level="j">Annals of Neurology</title><title level="j" type="abbrev">Ann Neurol.</title><idno type="pISSN">0364-5134</idno><idno type="eISSN">1531-8249</idno><idno type="DOI">10.1002/(ISSN)1531-8249</idno><imprint><publisher>John Wiley & Sons, Inc.</publisher><pubPlace>New York</pubPlace><date type="published" when="2000-07"></date><biblScope unit="volume">48</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="65">65</biblScope><biblScope unit="page" to="71">71</biblScope></imprint></monogr><idno type="istex">D02851CDA583E83DBB672D80151865CEC67EFA55</idno><idno type="DOI">10.1002/1531-8249(200007)48:1<65::AID-ANA10>3.0.CO;2-L</idno><idno type="ArticleID">ANA10</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2000</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>A gene for autosomal recessive parkinsonism, PARK2 (parkin), has recently been identified on chromosome 6q and shown to be mutated in Japanese and European families, mostly with early‐onset parkinsonism. Here we present a large pedigree from South Tyrol (a region of northern Italy) with adult‐onset, clinically typical tremor‐dominant parkinsonism of apparently autosomal dominant inheritance. Haplotype analysis excluded linkage to the chromosome 2p, 4p, and 4q regions that harbor genes associated with autosomal dominant parkinsonism, but implicated the parkin locus on chromosome 6q. Compound heterozygous deletions in the parkin gene (one large and one truncating) were identified in 4 affected male siblings. The patients were clinically indistinguishable from most patients with idiopathic Parkinson's disease. None of them displayed any of the clinical hallmarks described in patients with previously reported parkin mutations, including diurnal fluctuations, benefit from sleep, foot dystonia, hyperreflexia, and early susceptibility to levodopa‐induced dyskinesias. Two affected female individuals carried one (truncating) of the two deletions in a heterozygous state with an apparently normal allele. We conclude that the phenotypic spectrum associated with mutations in the parkin gene is broader than previously reported, suggesting that this gene may be important in the etiology of the more frequent late‐onset typical Parkinson's disease. 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number="7"></count></countGroup><titleGroup><title type="articleCategory">Original Article</title><title type="tocHeading1">Original Articles</title></titleGroup><copyright ownership="thirdParty">Copyright © 2000 American Neurological Association</copyright><eventGroup><event type="manuscriptReceived" date="2000-01-07"></event><event type="manuscriptRevised" date="2000-02-28"></event><event type="manuscriptAccepted" date="2000-02-29"></event><event type="firstOnline" date="2001-03-27"></event><event type="publishedOnlineFinalForm" date="2001-03-27"></event><event type="xmlConverted" agent="Converter:JWSART34_TO_WML3G version:2.3.15 mode:FullText source:HeaderRef result:HeaderRef" date="2010-07-19"></event><event type="xmlConverted" agent="Converter:WILEY_ML3G_TO_WILEY_ML3GV2 version:3.8.8" date="2014-01-03"></event><event type="xmlConverted" agent="Converter:WML3G_To_WML3G version:4.1.7 mode:FullText,remove_FC" date="2014-10-14"></event></eventGroup><numberingGroup><numbering type="pageFirst">65</numbering><numbering type="pageLast">71</numbering></numberingGroup><correspondenceTo>Molecular Genetics, AECOM, 1300 Morris Park Avenue, Bronx, NY 10461</correspondenceTo><linkGroup><link type="toTypesetVersion" href="file:ANA.ANA10.pdf"></link></linkGroup></publicationMeta><contentMeta><countGroup><count type="figureTotal" number="2"></count><count type="tableTotal" number="1"></count><count type="referenceTotal" number="35"></count><count type="wordTotal" number="4685"></count></countGroup><titleGroup><title type="main" xml:lang="en"><i>Parkin</i> deletions in a family with adult‐onset, tremor‐dominant parkinsonism: Expanding the phenotype</title><title type="short" xml:lang="en">Clinical and Genetic Study in Parkinson's Disease</title></titleGroup><creators><creator xml:id="au1" creatorRole="author" affiliationRef="#af1 #af2"><personName><givenNames>Christine</givenNames><familyName>Klein</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au2" creatorRole="author" affiliationRef="#af3"><personName><givenNames>Peter P.</givenNames><familyName>Pramstaller</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au3" creatorRole="author" affiliationRef="#af2 #af3"><personName><givenNames>Bernhard</givenNames><familyName>Kis</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au4" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Curtis C.</givenNames><familyName>Page</familyName><degrees>BA</degrees></personName></creator><creator xml:id="au5" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Martin</givenNames><familyName>Kann</familyName><degrees>BS</degrees></personName></creator><creator xml:id="au6" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Joanne</givenNames><familyName>Leung</familyName><degrees>BS</degrees></personName></creator><creator xml:id="au7" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Heather</givenNames><familyName>Woodward</familyName><degrees>BS</degrees></personName></creator><creator xml:id="au8" creatorRole="author" affiliationRef="#af4"><personName><givenNames>Claudio C.</givenNames><familyName>Castellan</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au9" creatorRole="author" affiliationRef="#af3"><personName><givenNames>Monika</givenNames><familyName>Scherer</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au10" creatorRole="author" affiliationRef="#af2"><personName><givenNames>Peter</givenNames><familyName>Vieregge</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au11" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Xandra O.</givenNames><familyName>Breakefield</familyName><degrees>PhD</degrees></personName></creator><creator xml:id="au12" creatorRole="author" affiliationRef="#af5"><personName><givenNames>Patricia L.</givenNames><familyName>Kramer</familyName><degrees>PhD</degrees></personName></creator><creator xml:id="au13" creatorRole="author" affiliationRef="#af1 #af6" corresponding="yes"><personName><givenNames>Laurie J.</givenNames><familyName>Ozelius</familyName><degrees>PhD</degrees></personName></creator></creators><affiliationGroup><affiliation xml:id="af1" countryCode="US" type="organization"><unparsedAffiliation>Molecular Neurogenetics Unit, Massachusetts General Hospital Departments of Neurology and Genetics and Neuroscience Program, Harvard Medical School, Boston, MA</unparsedAffiliation></affiliation><affiliation xml:id="af2" countryCode="DE" type="organization"><unparsedAffiliation>Department of Neurology, Medical University of Lübeck, Lübeck, Germany</unparsedAffiliation></affiliation><affiliation xml:id="af3" countryCode="IT" type="organization"><unparsedAffiliation>Department of Neurology, Regional General Hospital, Bolzano‐Bozen, Italy</unparsedAffiliation></affiliation><affiliation xml:id="af4" countryCode="IT" type="organization"><unparsedAffiliation>Department of Genetics, Regional General Hospital, Bolzano‐Bozen, Italy</unparsedAffiliation></affiliation><affiliation xml:id="af5" countryCode="US" type="organization"><unparsedAffiliation>Department of Neurology, Oregon Health Science University, Portland, OR</unparsedAffiliation></affiliation><affiliation xml:id="af6" countryCode="US" type="organization"><unparsedAffiliation>Molecular Genetics, Albert Einstein College of Medicine, Bronx, NY</unparsedAffiliation></affiliation></affiliationGroup><fundingInfo><fundingAgency>Neuroepidemiology Project South Tyrol/NEPT</fundingAgency></fundingInfo><fundingInfo><fundingAgency>Dystonia Medical Research Foundation</fundingAgency></fundingInfo><fundingInfo><fundingAgency>NINDS</fundingAgency><fundingNumber>NS38372</fundingNumber></fundingInfo><fundingInfo><fundingAgency>Deutsche Forschungsgemeinschaft</fundingAgency></fundingInfo><fundingInfo><fundingAgency>Blowitz‐Ridgeway Foundation</fundingAgency></fundingInfo><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><p>A gene for autosomal recessive parkinsonism, <i>PARK2</i> (<i>parkin</i>), has recently been identified on chromosome 6q and shown to be mutated in Japanese and European families, mostly with early‐onset parkinsonism. Here we present a large pedigree from South Tyrol (a region of northern Italy) with adult‐onset, clinically typical tremor‐dominant parkinsonism of apparently autosomal dominant inheritance. Haplotype analysis excluded linkage to the chromosome 2p, 4p, and 4q regions that harbor genes associated with autosomal dominant parkinsonism, but implicated the <i>parkin</i> locus on chromosome 6q. Compound heterozygous deletions in the <i>parkin</i> gene (one large and one truncating) were identified in 4 affected male siblings. The patients were clinically indistinguishable from most patients with idiopathic Parkinson's disease. None of them displayed any of the clinical hallmarks described in patients with previously reported <i>parkin</i> mutations, including diurnal fluctuations, benefit from sleep, foot dystonia, hyperreflexia, and early susceptibility to levodopa‐induced dyskinesias. Two affected female individuals carried one (truncating) of the two deletions in a heterozygous state with an apparently normal allele. We conclude that the phenotypic spectrum associated with mutations in the <i>parkin</i> gene is broader than previously reported, suggesting that this gene may be important in the etiology of the more frequent late‐onset typical Parkinson's disease. Ann Neurol 2000;48:65–71</p></abstract></abstractGroup></contentMeta></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Parkin deletions in a family with adult‐onset, tremor‐dominant parkinsonism: Expanding the phenotype</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>Clinical and Genetic Study in Parkinson's Disease</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>deletions in a family with adult‐onset, tremor‐dominant parkinsonism: Expanding the phenotype</title></titleInfo><name type="personal"><namePart type="given">Christine</namePart><namePart type="family">Klein</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Molecular Neurogenetics Unit, Massachusetts General Hospital Departments of Neurology and Genetics and Neuroscience Program, Harvard Medical School, Boston, MA</affiliation><affiliation>Department of Neurology, Medical University of Lübeck, Lübeck, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Peter P.</namePart><namePart type="family">Pramstaller</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neurology, Regional General Hospital, Bolzano‐Bozen, Italy</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Bernhard</namePart><namePart type="family">Kis</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neurology, Medical University of Lübeck, Lübeck, Germany</affiliation><affiliation>Department of Neurology, Regional General Hospital, Bolzano‐Bozen, Italy</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Curtis C.</namePart><namePart type="family">Page</namePart><namePart type="termsOfAddress">BA</namePart><affiliation>Molecular Neurogenetics Unit, Massachusetts General Hospital Departments of Neurology and Genetics and Neuroscience Program, Harvard Medical School, Boston, MA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Martin</namePart><namePart type="family">Kann</namePart><namePart type="termsOfAddress">BS</namePart><affiliation>Molecular Neurogenetics Unit, Massachusetts General Hospital Departments of Neurology and Genetics and Neuroscience Program, Harvard Medical School, Boston, MA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Joanne</namePart><namePart type="family">Leung</namePart><namePart type="termsOfAddress">BS</namePart><affiliation>Molecular Neurogenetics Unit, Massachusetts General Hospital Departments of Neurology and Genetics and Neuroscience Program, Harvard Medical School, Boston, MA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Heather</namePart><namePart type="family">Woodward</namePart><namePart type="termsOfAddress">BS</namePart><affiliation>Molecular Neurogenetics Unit, Massachusetts General Hospital Departments of Neurology and Genetics and Neuroscience Program, Harvard Medical School, Boston, MA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Claudio C.</namePart><namePart type="family">Castellan</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Genetics, Regional General Hospital, Bolzano‐Bozen, Italy</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Monika</namePart><namePart type="family">Scherer</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neurology, Regional General Hospital, Bolzano‐Bozen, Italy</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Peter</namePart><namePart type="family">Vieregge</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neurology, Medical University of Lübeck, Lübeck, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Xandra O.</namePart><namePart type="family">Breakefield</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Molecular Neurogenetics Unit, Massachusetts General Hospital Departments of Neurology and Genetics and Neuroscience Program, Harvard Medical School, Boston, MA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Patricia L.</namePart><namePart type="family">Kramer</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Department of Neurology, Oregon Health Science University, Portland, OR</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Laurie J.</namePart><namePart type="family">Ozelius</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Molecular Neurogenetics Unit, Massachusetts General Hospital Departments of Neurology and Genetics and Neuroscience Program, Harvard Medical School, Boston, MA</affiliation><affiliation>Molecular Genetics, Albert Einstein College of Medicine, Bronx, NY</affiliation><description>Correspondence: Molecular Genetics, AECOM, 1300 Morris Park Avenue, Bronx, NY 10461</description><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">2000-07</dateIssued><dateCaptured encoding="w3cdtf">2000-01-07</dateCaptured><dateValid encoding="w3cdtf">2000-02-29</dateValid><copyrightDate encoding="w3cdtf">2000</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">2</extent><extent unit="tables">1</extent><extent unit="references">35</extent><extent unit="words">4685</extent></physicalDescription><abstract lang="en">A gene for autosomal recessive parkinsonism, PARK2 (parkin), has recently been identified on chromosome 6q and shown to be mutated in Japanese and European families, mostly with early‐onset parkinsonism. Here we present a large pedigree from South Tyrol (a region of northern Italy) with adult‐onset, clinically typical tremor‐dominant parkinsonism of apparently autosomal dominant inheritance. Haplotype analysis excluded linkage to the chromosome 2p, 4p, and 4q regions that harbor genes associated with autosomal dominant parkinsonism, but implicated the parkin locus on chromosome 6q. Compound heterozygous deletions in the parkin gene (one large and one truncating) were identified in 4 affected male siblings. The patients were clinically indistinguishable from most patients with idiopathic Parkinson's disease. None of them displayed any of the clinical hallmarks described in patients with previously reported parkin mutations, including diurnal fluctuations, benefit from sleep, foot dystonia, hyperreflexia, and early susceptibility to levodopa‐induced dyskinesias. Two affected female individuals carried one (truncating) of the two deletions in a heterozygous state with an apparently normal allele. We conclude that the phenotypic spectrum associated with mutations in the parkin gene is broader than previously reported, suggesting that this gene may be important in the etiology of the more frequent late‐onset typical Parkinson's disease. Ann Neurol 2000;48:65–71</abstract><note type="funding">Neuroepidemiology Project South Tyrol/NEPT</note><note type="funding">Dystonia Medical Research Foundation</note><note type="funding">NINDS - No. NS38372; </note><note type="funding">Deutsche Forschungsgemeinschaft</note><note type="funding">Blowitz‐Ridgeway Foundation</note><relatedItem type="host"><titleInfo><title>Annals of Neurology</title></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>2000</date><detail type="volume"><caption>vol.</caption><number>48</number></detail><detail type="issue"><caption>no.</caption><number>1</number></detail><extent unit="pages"><start>65</start><end>71</end><total>7</total></extent></part></relatedItem><identifier type="istex">D02851CDA583E83DBB672D80151865CEC67EFA55</identifier><identifier type="DOI">10.1002/1531-8249(200007)48:1<65::AID-ANA10>3.0.CO;2-L</identifier><identifier type="ArticleID">ANA10</identifier><accessCondition type="use and reproduction" contentType="copyright">Copyright © 2000 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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