Genotypic and phenotypic characteristics of Dutch patients with early onset Parkinson's disease.
Identifieur interne : 001D93 ( PubMed/Checkpoint ); précédent : 001D92; suivant : 001D94Genotypic and phenotypic characteristics of Dutch patients with early onset Parkinson's disease.
Auteurs : Maria G. Macedo [Pays-Bas] ; Dagmar Verbaan ; Yue Fang ; Stephanie M. Van Rooden ; Martine Visser ; Burcu Anar ; Antonella Uras ; Justus L. Groen ; Patrizia Rizzu ; Jacobus J. Van Hilten ; Peter HeutinkSource :
- Movement disorders : official journal of the Movement Disorder Society [ 1531-8257 ] ; 2009.
Descripteurs français
- Wicri :
- geographic : Pays-Bas.
English descriptors
- KwdEn :
- Adolescent, Adult, Age of Onset, Amino Acid Sequence, Conserved Sequence, DNA Mutational Analysis, Female, Genotype, Humans, Intracellular Signaling Peptides and Proteins (genetics), Male, Middle Aged, Molecular Sequence Data, Netherlands (epidemiology), Oncogene Proteins (genetics), Parkinson Disease (epidemiology), Parkinson Disease (genetics), Parkinsonian Disorders (epidemiology), Parkinsonian Disorders (genetics), Phenotype, Protein Kinases (genetics), Protein-Serine-Threonine Kinases (genetics), Sequence Alignment, Sequence Homology, Nucleic Acid, Ubiquitin-Protein Ligases (genetics), Young Adult, alpha-Synuclein (genetics).
- MESH :
- chemical , genetics : Intracellular Signaling Peptides and Proteins, Oncogene Proteins, Protein Kinases, Protein-Serine-Threonine Kinases, Ubiquitin-Protein Ligases, alpha-Synuclein.
- geographic , epidemiology : Netherlands.
- epidemiology : Parkinson Disease, Parkinsonian Disorders.
- genetics : Parkinson Disease, Parkinsonian Disorders.
- Adolescent, Adult, Age of Onset, Amino Acid Sequence, Conserved Sequence, DNA Mutational Analysis, Female, Genotype, Humans, Male, Middle Aged, Molecular Sequence Data, Phenotype, Sequence Alignment, Sequence Homology, Nucleic Acid, Young Adult.
Abstract
Early onset Parkinson's disease (EOPD) has been associated with mutations in the Parkin, DJ-1, PINK1, LRRK2, and SNCA genes. The aim of this study is to assess the contribution of these genes in a Dutch EOPD cohort and the phenotypic characteristics of the mutation carriers. A total of 187 unrelated Dutch EOPD patients (age at onset < or = 50 years) were phenotyped and screened for mutations in all exons of Parkin, DJ-1, and PINK1 by direct sequencing and gene dosage analysis. Additionally, analysis of the A30P mutation and exon dosage of SNCA and sequencing of exons 19,31,35,38,41, and 48 of LRRK2 was performed. Pathogenic variations could explain disease in 4% (7 of 187) of the patients including five patients carrying homozygous or compound heterozygous mutations in Parkin, one with a novel homozygous deletion in DJ-1 (P158Del) and one with a heterozygous mutation in LRRK2 (T2356I). We found seven novel mutations. The phenotypic characteristics of mutation carriers varied widely, comparable to the variability seen in sporadic EOPD. Parkin is the most frequently mutated gene in this EOPD cohort, followed by DJ-1, PINK1 and LRRK2. The low overall mutation frequency indicates that the extrapolation of mutation frequencies from other populations should be applied with caution.
DOI: 10.1002/mds.22287
PubMed: 18973254
Affiliations:
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Macedo</name><affiliation wicri:level="3"><nlm:affiliation>Section of Medical Genomics, Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands. m.macedo@vumc.nl</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Section of Medical Genomics, Department of Clinical Genetics, VU University Medical Center, Amsterdam</wicri:regionArea><placeName><settlement type="city">Amsterdam</settlement><region nuts="2" type="province">Hollande-Septentrionale</region></placeName></affiliation></author><author><name sortKey="Verbaan, Dagmar" sort="Verbaan, Dagmar" uniqKey="Verbaan D" first="Dagmar" last="Verbaan">Dagmar Verbaan</name></author><author><name sortKey="Fang, Yue" sort="Fang, Yue" uniqKey="Fang Y" first="Yue" last="Fang">Yue Fang</name></author><author><name sortKey="Van Rooden, Stephanie M" sort="Van Rooden, Stephanie M" uniqKey="Van Rooden S" first="Stephanie M" last="Van Rooden">Stephanie M. Van Rooden</name></author><author><name sortKey="Visser, Martine" sort="Visser, Martine" uniqKey="Visser M" first="Martine" last="Visser">Martine Visser</name></author><author><name sortKey="Anar, Burcu" sort="Anar, Burcu" uniqKey="Anar B" first="Burcu" last="Anar">Burcu Anar</name></author><author><name sortKey="Uras, Antonella" sort="Uras, Antonella" uniqKey="Uras A" first="Antonella" last="Uras">Antonella Uras</name></author><author><name sortKey="Groen, Justus L" sort="Groen, Justus L" uniqKey="Groen J" first="Justus L" last="Groen">Justus L. Groen</name></author><author><name sortKey="Rizzu, Patrizia" sort="Rizzu, Patrizia" uniqKey="Rizzu P" first="Patrizia" last="Rizzu">Patrizia Rizzu</name></author><author><name sortKey="Van Hilten, Jacobus J" sort="Van Hilten, Jacobus J" uniqKey="Van Hilten J" first="Jacobus J" last="Van Hilten">Jacobus J. 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Macedo</name><affiliation wicri:level="3"><nlm:affiliation>Section of Medical Genomics, Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands. m.macedo@vumc.nl</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Section of Medical Genomics, Department of Clinical Genetics, VU University Medical Center, Amsterdam</wicri:regionArea><placeName><settlement type="city">Amsterdam</settlement><region nuts="2" type="province">Hollande-Septentrionale</region></placeName></affiliation></author><author><name sortKey="Verbaan, Dagmar" sort="Verbaan, Dagmar" uniqKey="Verbaan D" first="Dagmar" last="Verbaan">Dagmar Verbaan</name></author><author><name sortKey="Fang, Yue" sort="Fang, Yue" uniqKey="Fang Y" first="Yue" last="Fang">Yue Fang</name></author><author><name sortKey="Van Rooden, Stephanie M" sort="Van Rooden, Stephanie M" uniqKey="Van Rooden S" first="Stephanie M" last="Van Rooden">Stephanie M. Van Rooden</name></author><author><name sortKey="Visser, Martine" sort="Visser, Martine" uniqKey="Visser M" first="Martine" last="Visser">Martine Visser</name></author><author><name sortKey="Anar, Burcu" sort="Anar, Burcu" uniqKey="Anar B" first="Burcu" last="Anar">Burcu Anar</name></author><author><name sortKey="Uras, Antonella" sort="Uras, Antonella" uniqKey="Uras A" first="Antonella" last="Uras">Antonella Uras</name></author><author><name sortKey="Groen, Justus L" sort="Groen, Justus L" uniqKey="Groen J" first="Justus L" last="Groen">Justus L. Groen</name></author><author><name sortKey="Rizzu, Patrizia" sort="Rizzu, Patrizia" uniqKey="Rizzu P" first="Patrizia" last="Rizzu">Patrizia Rizzu</name></author><author><name sortKey="Van Hilten, Jacobus J" sort="Van Hilten, Jacobus J" uniqKey="Van Hilten J" first="Jacobus J" last="Van Hilten">Jacobus J. Van Hilten</name></author><author><name sortKey="Heutink, Peter" sort="Heutink, Peter" uniqKey="Heutink P" first="Peter" last="Heutink">Peter Heutink</name></author></analytic><series><title level="j">Movement disorders : official journal of the Movement Disorder Society</title><idno type="eISSN">1531-8257</idno><imprint><date when="2009" type="published">2009</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adolescent</term><term>Adult</term><term>Age of Onset</term><term>Amino Acid Sequence</term><term>Conserved Sequence</term><term>DNA Mutational Analysis</term><term>Female</term><term>Genotype</term><term>Humans</term><term>Intracellular Signaling Peptides and Proteins (genetics)</term><term>Male</term><term>Middle Aged</term><term>Molecular Sequence Data</term><term>Netherlands (epidemiology)</term><term>Oncogene Proteins (genetics)</term><term>Parkinson Disease (epidemiology)</term><term>Parkinson Disease (genetics)</term><term>Parkinsonian Disorders (epidemiology)</term><term>Parkinsonian Disorders (genetics)</term><term>Phenotype</term><term>Protein Kinases (genetics)</term><term>Protein-Serine-Threonine Kinases (genetics)</term><term>Sequence Alignment</term><term>Sequence Homology, Nucleic Acid</term><term>Ubiquitin-Protein Ligases (genetics)</term><term>Young Adult</term><term>alpha-Synuclein (genetics)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Intracellular Signaling Peptides and Proteins</term><term>Oncogene Proteins</term><term>Protein Kinases</term><term>Protein-Serine-Threonine Kinases</term><term>Ubiquitin-Protein Ligases</term><term>alpha-Synuclein</term></keywords><keywords scheme="MESH" type="geographic" qualifier="epidemiology" xml:lang="en"><term>Netherlands</term></keywords><keywords scheme="MESH" qualifier="epidemiology" xml:lang="en"><term>Parkinson Disease</term><term>Parkinsonian Disorders</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Parkinson Disease</term><term>Parkinsonian Disorders</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adolescent</term><term>Adult</term><term>Age of Onset</term><term>Amino Acid Sequence</term><term>Conserved Sequence</term><term>DNA Mutational Analysis</term><term>Female</term><term>Genotype</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>Molecular Sequence Data</term><term>Phenotype</term><term>Sequence Alignment</term><term>Sequence Homology, Nucleic Acid</term><term>Young Adult</term></keywords><keywords scheme="Wicri" type="geographic" xml:lang="fr"><term>Pays-Bas</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Early onset Parkinson's disease (EOPD) has been associated with mutations in the Parkin, DJ-1, PINK1, LRRK2, and SNCA genes. The aim of this study is to assess the contribution of these genes in a Dutch EOPD cohort and the phenotypic characteristics of the mutation carriers. A total of 187 unrelated Dutch EOPD patients (age at onset < or = 50 years) were phenotyped and screened for mutations in all exons of Parkin, DJ-1, and PINK1 by direct sequencing and gene dosage analysis. Additionally, analysis of the A30P mutation and exon dosage of SNCA and sequencing of exons 19,31,35,38,41, and 48 of LRRK2 was performed. Pathogenic variations could explain disease in 4% (7 of 187) of the patients including five patients carrying homozygous or compound heterozygous mutations in Parkin, one with a novel homozygous deletion in DJ-1 (P158Del) and one with a heterozygous mutation in LRRK2 (T2356I). We found seven novel mutations. The phenotypic characteristics of mutation carriers varied widely, comparable to the variability seen in sporadic EOPD. Parkin is the most frequently mutated gene in this EOPD cohort, followed by DJ-1, PINK1 and LRRK2. The low overall mutation frequency indicates that the extrapolation of mutation frequencies from other populations should be applied with caution.</div></front></TEI><pubmed><MedlineCitation Owner="NLM" Status="MEDLINE"><PMID Version="1">18973254</PMID><DateCreated><Year>2009</Year><Month>02</Month><Day>02</Day></DateCreated><DateCompleted><Year>2009</Year><Month>06</Month><Day>08</Day></DateCompleted><DateRevised><Year>2012</Year><Month>06</Month><Day>25</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1531-8257</ISSN><JournalIssue CitedMedium="Internet"><Volume>24</Volume><Issue>2</Issue><PubDate><Year>2009</Year><Month>Jan</Month><Day>30</Day></PubDate></JournalIssue><Title>Movement disorders : official journal of the Movement Disorder Society</Title><ISOAbbreviation>Mov. Disord.</ISOAbbreviation></Journal><ArticleTitle>Genotypic and phenotypic characteristics of Dutch patients with early onset Parkinson's disease.</ArticleTitle><Pagination><MedlinePgn>196-203</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1002/mds.22287</ELocationID><Abstract><AbstractText>Early onset Parkinson's disease (EOPD) has been associated with mutations in the Parkin, DJ-1, PINK1, LRRK2, and SNCA genes. The aim of this study is to assess the contribution of these genes in a Dutch EOPD cohort and the phenotypic characteristics of the mutation carriers. A total of 187 unrelated Dutch EOPD patients (age at onset < or = 50 years) were phenotyped and screened for mutations in all exons of Parkin, DJ-1, and PINK1 by direct sequencing and gene dosage analysis. Additionally, analysis of the A30P mutation and exon dosage of SNCA and sequencing of exons 19,31,35,38,41, and 48 of LRRK2 was performed. Pathogenic variations could explain disease in 4% (7 of 187) of the patients including five patients carrying homozygous or compound heterozygous mutations in Parkin, one with a novel homozygous deletion in DJ-1 (P158Del) and one with a heterozygous mutation in LRRK2 (T2356I). We found seven novel mutations. The phenotypic characteristics of mutation carriers varied widely, comparable to the variability seen in sporadic EOPD. Parkin is the most frequently mutated gene in this EOPD cohort, followed by DJ-1, PINK1 and LRRK2. The low overall mutation frequency indicates that the extrapolation of mutation frequencies from other populations should be applied with caution.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Macedo</LastName><ForeName>Maria G</ForeName><Initials>MG</Initials><AffiliationInfo><Affiliation>Section of Medical Genomics, Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands. m.macedo@vumc.nl</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Verbaan</LastName><ForeName>Dagmar</ForeName><Initials>D</Initials></Author><Author ValidYN="Y"><LastName>Fang</LastName><ForeName>Yue</ForeName><Initials>Y</Initials></Author><Author ValidYN="Y"><LastName>van Rooden</LastName><ForeName>Stephanie M</ForeName><Initials>SM</Initials></Author><Author ValidYN="Y"><LastName>Visser</LastName><ForeName>Martine</ForeName><Initials>M</Initials></Author><Author ValidYN="Y"><LastName>Anar</LastName><ForeName>Burcu</ForeName><Initials>B</Initials></Author><Author ValidYN="Y"><LastName>Uras</LastName><ForeName>Antonella</ForeName><Initials>A</Initials></Author><Author ValidYN="Y"><LastName>Groen</LastName><ForeName>Justus L</ForeName><Initials>JL</Initials></Author><Author ValidYN="Y"><LastName>Rizzu</LastName><ForeName>Patrizia</ForeName><Initials>P</Initials></Author><Author ValidYN="Y"><LastName>van Hilten</LastName><ForeName>Jacobus J</ForeName><Initials>JJ</Initials></Author><Author ValidYN="Y"><LastName>Heutink</LastName><ForeName>Peter</ForeName><Initials>P</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Mov 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human</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.11.1</RegistryNumber><NameOfSubstance UI="C433927">PTEN-induced putative kinase</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.11.1</RegistryNumber><NameOfSubstance UI="D017346">Protein-Serine-Threonine Kinases</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 6.3.2.19</RegistryNumber><NameOfSubstance UI="D044767">Ubiquitin-Protein Ligases</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 6.3.2.19</RegistryNumber><NameOfSubstance UI="C111567">parkin protein</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName MajorTopicYN="N" UI="D000293">Adolescent</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D000328">Adult</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D017668">Age of Onset</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D000595">Amino Acid Sequence</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D017124">Conserved Sequence</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D004252">DNA Mutational Analysis</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D005260">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D005838">Genotype</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D006801">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D047908">Intracellular Signaling Peptides and Proteins</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000235">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D008297">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D008875">Middle 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UI="Q000235">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D010641">Phenotype</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D011494">Protein Kinases</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000235">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D017346">Protein-Serine-Threonine Kinases</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000235">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D016415">Sequence Alignment</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D012689">Sequence Homology, Nucleic Acid</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D044767">Ubiquitin-Protein Ligases</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000235">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D055815">Young Adult</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D051844">alpha-Synuclein</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000235">genetics</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2008</Year><Month>11</Month><Day>1</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2009</Year><Month>6</Month><Day>9</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2008</Year><Month>11</Month><Day>1</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="doi">10.1002/mds.22287</ArticleId><ArticleId IdType="pubmed">18973254</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Pays-Bas</li></country><region><li>Hollande-Septentrionale</li></region><settlement><li>Amsterdam</li></settlement></list><tree><noCountry><name sortKey="Anar, Burcu" sort="Anar, Burcu" uniqKey="Anar B" first="Burcu" last="Anar">Burcu Anar</name><name sortKey="Fang, Yue" sort="Fang, Yue" uniqKey="Fang Y" first="Yue" last="Fang">Yue Fang</name><name sortKey="Groen, Justus L" sort="Groen, Justus L" uniqKey="Groen J" first="Justus L" last="Groen">Justus L. Groen</name><name sortKey="Heutink, Peter" sort="Heutink, Peter" uniqKey="Heutink P" first="Peter" last="Heutink">Peter Heutink</name><name sortKey="Rizzu, Patrizia" sort="Rizzu, Patrizia" uniqKey="Rizzu P" first="Patrizia" last="Rizzu">Patrizia Rizzu</name><name sortKey="Uras, Antonella" sort="Uras, Antonella" uniqKey="Uras A" first="Antonella" last="Uras">Antonella Uras</name><name sortKey="Van Hilten, Jacobus J" sort="Van Hilten, Jacobus J" uniqKey="Van Hilten J" first="Jacobus J" last="Van Hilten">Jacobus J. Van Hilten</name><name sortKey="Van Rooden, Stephanie M" sort="Van Rooden, Stephanie M" uniqKey="Van Rooden S" first="Stephanie M" last="Van Rooden">Stephanie M. Van Rooden</name><name sortKey="Verbaan, Dagmar" sort="Verbaan, Dagmar" uniqKey="Verbaan D" first="Dagmar" last="Verbaan">Dagmar Verbaan</name><name sortKey="Visser, Martine" sort="Visser, Martine" uniqKey="Visser M" first="Martine" last="Visser">Martine Visser</name></noCountry><country name="Pays-Bas"><region name="Hollande-Septentrionale"><name sortKey="Macedo, Maria G" sort="Macedo, Maria G" uniqKey="Macedo M" first="Maria G" last="Macedo">Maria G. Macedo</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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