Linkage exclusion in French families with probable Parkinson' s disease.
Identifieur interne : 000375 ( Ncbi/Merge ); précédent : 000374; suivant : 000376Linkage exclusion in French families with probable Parkinson' s disease.
Auteurs : M. Farrer [États-Unis] ; T. Destée ; E. Becquet ; F. Wavrant-De Vrièze ; V. Mouroux ; F. Richard ; L. Defebvre ; S. Lincoln ; J. Hardy ; P. Amouyel ; M C Chartier-HarlinSource :
- Movement disorders : official journal of the Movement Disorder Society [ 0885-3185 ] ; 2000.
Descripteurs français
- Wicri :
- geographic : France.
English descriptors
- KwdEn :
- Adult, Age of Onset, Aged, Chromosomes, Human, Pair 17 (genetics), Chromosomes, Human, Pair 2 (genetics), Chromosomes, Human, Pair 4 (genetics), Chromosomes, Human, Pair 6 (genetics), Cluster Analysis, Female, France, Genetic Linkage, Haplotypes, Humans, Ligases (genetics), Male, Middle Aged, Mutation, Nerve Tissue Proteins (genetics), Parkinson Disease (diagnosis), Parkinson Disease (genetics), Pedigree, Sex Distribution, Synucleins, Thiolester Hydrolases (genetics), Ubiquitin Thiolesterase, Ubiquitin-Protein Ligases, alpha-Synuclein, tau Proteins (genetics).
- MESH :
- chemical , genetics : Ligases, Nerve Tissue Proteins, Thiolester Hydrolases, tau Proteins.
- geographic : France, Synucleins, Ubiquitin Thiolesterase, Ubiquitin-Protein Ligases, alpha-Synuclein.
- diagnosis : Parkinson Disease.
- genetics : Chromosomes, Human, Pair 17, Chromosomes, Human, Pair 2, Chromosomes, Human, Pair 4, Chromosomes, Human, Pair 6, Parkinson Disease.
- Adult, Age of Onset, Aged, Cluster Analysis, Female, Genetic Linkage, Haplotypes, Humans, Male, Middle Aged, Mutation, Pedigree, Sex Distribution.
Abstract
We analyzed the segregation of genetic markers spanning chromosomal regions 2p13, 4p14-15, 4q21-23, 6q25-27, and 17q21 in nine French families affected by autosomal-dominant probable Parkinson's disease. These regions have been linked or associated with familial Parkinson's disease. Multipoint linkage and haplotype analyses excluded 2p13 and 4p14-15 loci in five of nine families. For three families, which were equivocal for two-point linkage at D4S405, the ubiquitin carboxy-terminal hydrolase gene (UCH-L1) was sequenced. In one family, a novel UCH-L1 M124L mutation that did not segregate with early-onset disease was identified. This suggests that rare variants in this gene may not be pathogenic. In seven of nine families, it could be inferred that affected individuals did not share 4q21-23 (alpha-synuclein) haplotypes. All families were unequivocally excluded by haplotype analysis from the parkin locus on 6q25-27. Finally, the 17q21 region was excluded in four of nine families, and no mutation in the tau gene was identified in the five remaining families. Findings from this study confirm genetic heterogeneity within familial parkinsonism.
PubMed: 11104189
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pubmed:11104189Le document en format XML
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Wavrant-De Vrièze</name></author><author><name sortKey="Mouroux, V" sort="Mouroux, V" uniqKey="Mouroux V" first="V" last="Mouroux">V. Mouroux</name></author><author><name sortKey="Richard, F" sort="Richard, F" uniqKey="Richard F" first="F" last="Richard">F. Richard</name></author><author><name sortKey="Defebvre, L" sort="Defebvre, L" uniqKey="Defebvre L" first="L" last="Defebvre">L. Defebvre</name></author><author><name sortKey="Lincoln, S" sort="Lincoln, S" uniqKey="Lincoln S" first="S" last="Lincoln">S. Lincoln</name></author><author><name sortKey="Hardy, J" sort="Hardy, J" uniqKey="Hardy J" first="J" last="Hardy">J. Hardy</name></author><author><name sortKey="Amouyel, P" sort="Amouyel, P" uniqKey="Amouyel P" first="P" last="Amouyel">P. Amouyel</name></author><author><name sortKey="Chartier Harlin, M C" sort="Chartier Harlin, M C" uniqKey="Chartier Harlin M" first="M C" last="Chartier-Harlin">M C Chartier-Harlin</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2000">2000</date><idno type="RBID">pubmed:11104189</idno><idno type="pmid">11104189</idno><idno type="wicri:Area/PubMed/Corpus">003E76</idno><idno type="wicri:Area/PubMed/Curation">003E76</idno><idno type="wicri:Area/PubMed/Checkpoint">003F47</idno><idno type="wicri:Area/Ncbi/Merge">000375</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Linkage exclusion in French families with probable Parkinson' s disease.</title><author><name sortKey="Farrer, M" sort="Farrer, M" uniqKey="Farrer M" first="M" last="Farrer">M. Farrer</name><affiliation wicri:level="2"><nlm:affiliation>Neurogenetics Laboratory, Mayo Clinic Jacksonville, Florida, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Neurogenetics Laboratory, Mayo Clinic Jacksonville, Florida</wicri:regionArea><placeName><region type="state">Floride</region></placeName></affiliation></author><author><name sortKey="Destee, T" sort="Destee, T" uniqKey="Destee T" first="T" last="Destée">T. Destée</name></author><author><name sortKey="Becquet, E" sort="Becquet, E" uniqKey="Becquet E" first="E" last="Becquet">E. Becquet</name></author><author><name sortKey="Wavrant De Vrieze, F" sort="Wavrant De Vrieze, F" uniqKey="Wavrant De Vrieze F" first="F" last="Wavrant-De Vrièze">F. Wavrant-De Vrièze</name></author><author><name sortKey="Mouroux, V" sort="Mouroux, V" uniqKey="Mouroux V" first="V" last="Mouroux">V. Mouroux</name></author><author><name sortKey="Richard, F" sort="Richard, F" uniqKey="Richard F" first="F" last="Richard">F. Richard</name></author><author><name sortKey="Defebvre, L" sort="Defebvre, L" uniqKey="Defebvre L" first="L" last="Defebvre">L. Defebvre</name></author><author><name sortKey="Lincoln, S" sort="Lincoln, S" uniqKey="Lincoln S" first="S" last="Lincoln">S. Lincoln</name></author><author><name sortKey="Hardy, J" sort="Hardy, J" uniqKey="Hardy J" first="J" last="Hardy">J. Hardy</name></author><author><name sortKey="Amouyel, P" sort="Amouyel, P" uniqKey="Amouyel P" first="P" last="Amouyel">P. Amouyel</name></author><author><name sortKey="Chartier Harlin, M C" sort="Chartier Harlin, M C" uniqKey="Chartier Harlin M" first="M C" last="Chartier-Harlin">M C Chartier-Harlin</name></author></analytic><series><title level="j">Movement disorders : official journal of the Movement Disorder Society</title><idno type="ISSN">0885-3185</idno><imprint><date when="2000" type="published">2000</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term><term>Age of Onset</term><term>Aged</term><term>Chromosomes, Human, Pair 17 (genetics)</term><term>Chromosomes, Human, Pair 2 (genetics)</term><term>Chromosomes, Human, Pair 4 (genetics)</term><term>Chromosomes, Human, Pair 6 (genetics)</term><term>Cluster Analysis</term><term>Female</term><term>France</term><term>Genetic Linkage</term><term>Haplotypes</term><term>Humans</term><term>Ligases (genetics)</term><term>Male</term><term>Middle Aged</term><term>Mutation</term><term>Nerve Tissue Proteins (genetics)</term><term>Parkinson Disease (diagnosis)</term><term>Parkinson Disease (genetics)</term><term>Pedigree</term><term>Sex Distribution</term><term>Synucleins</term><term>Thiolester Hydrolases (genetics)</term><term>Ubiquitin Thiolesterase</term><term>Ubiquitin-Protein Ligases</term><term>alpha-Synuclein</term><term>tau Proteins (genetics)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Ligases</term><term>Nerve Tissue Proteins</term><term>Thiolester Hydrolases</term><term>tau Proteins</term></keywords><keywords scheme="MESH" type="geographic" xml:lang="en"><term>France</term><term>Synucleins</term><term>Ubiquitin Thiolesterase</term><term>Ubiquitin-Protein Ligases</term><term>alpha-Synuclein</term></keywords><keywords scheme="MESH" qualifier="diagnosis" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Chromosomes, Human, Pair 17</term><term>Chromosomes, Human, Pair 2</term><term>Chromosomes, Human, Pair 4</term><term>Chromosomes, Human, Pair 6</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adult</term><term>Age of Onset</term><term>Aged</term><term>Cluster Analysis</term><term>Female</term><term>Genetic Linkage</term><term>Haplotypes</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>Mutation</term><term>Pedigree</term><term>Sex Distribution</term></keywords><keywords scheme="Wicri" type="geographic" xml:lang="fr"><term>France</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">We analyzed the segregation of genetic markers spanning chromosomal regions 2p13, 4p14-15, 4q21-23, 6q25-27, and 17q21 in nine French families affected by autosomal-dominant probable Parkinson's disease. These regions have been linked or associated with familial Parkinson's disease. Multipoint linkage and haplotype analyses excluded 2p13 and 4p14-15 loci in five of nine families. For three families, which were equivocal for two-point linkage at D4S405, the ubiquitin carboxy-terminal hydrolase gene (UCH-L1) was sequenced. In one family, a novel UCH-L1 M124L mutation that did not segregate with early-onset disease was identified. This suggests that rare variants in this gene may not be pathogenic. In seven of nine families, it could be inferred that affected individuals did not share 4q21-23 (alpha-synuclein) haplotypes. All families were unequivocally excluded by haplotype analysis from the parkin locus on 6q25-27. Finally, the 17q21 region was excluded in four of nine families, and no mutation in the tau gene was identified in the five remaining families. Findings from this study confirm genetic heterogeneity within familial parkinsonism.</div></front></TEI><pubmed><MedlineCitation Owner="NLM" Status="MEDLINE"><PMID Version="1">11104189</PMID><DateCreated><Year>2001</Year><Month>03</Month><Day>07</Day></DateCreated><DateCompleted><Year>2001</Year><Month>05</Month><Day>31</Day></DateCompleted><DateRevised><Year>2010</Year><Month>11</Month><Day>18</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0885-3185</ISSN><JournalIssue CitedMedium="Print"><Volume>15</Volume><Issue>6</Issue><PubDate><Year>2000</Year><Month>Nov</Month></PubDate></JournalIssue><Title>Movement disorders : official journal of the Movement Disorder Society</Title><ISOAbbreviation>Mov. Disord.</ISOAbbreviation></Journal><ArticleTitle>Linkage exclusion in French families with probable Parkinson' s disease.</ArticleTitle><Pagination><MedlinePgn>1075-83</MedlinePgn></Pagination><Abstract><AbstractText>We analyzed the segregation of genetic markers spanning chromosomal regions 2p13, 4p14-15, 4q21-23, 6q25-27, and 17q21 in nine French families affected by autosomal-dominant probable Parkinson's disease. These regions have been linked or associated with familial Parkinson's disease. Multipoint linkage and haplotype analyses excluded 2p13 and 4p14-15 loci in five of nine families. For three families, which were equivocal for two-point linkage at D4S405, the ubiquitin carboxy-terminal hydrolase gene (UCH-L1) was sequenced. In one family, a novel UCH-L1 M124L mutation that did not segregate with early-onset disease was identified. This suggests that rare variants in this gene may not be pathogenic. In seven of nine families, it could be inferred that affected individuals did not share 4q21-23 (alpha-synuclein) haplotypes. All families were unequivocally excluded by haplotype analysis from the parkin locus on 6q25-27. Finally, the 17q21 region was excluded in four of nine families, and no mutation in the tau gene was identified in the five remaining families. Findings from this study confirm genetic heterogeneity within familial parkinsonism.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Farrer</LastName><ForeName>M</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Neurogenetics Laboratory, Mayo Clinic Jacksonville, Florida, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Destée</LastName><ForeName>T</ForeName><Initials>T</Initials></Author><Author ValidYN="Y"><LastName>Becquet</LastName><ForeName>E</ForeName><Initials>E</Initials></Author><Author ValidYN="Y"><LastName>Wavrant-De Vrièze</LastName><ForeName>F</ForeName><Initials>F</Initials></Author><Author ValidYN="Y"><LastName>Mouroux</LastName><ForeName>V</ForeName><Initials>V</Initials></Author><Author ValidYN="Y"><LastName>Richard</LastName><ForeName>F</ForeName><Initials>F</Initials></Author><Author ValidYN="Y"><LastName>Defebvre</LastName><ForeName>L</ForeName><Initials>L</Initials></Author><Author ValidYN="Y"><LastName>Lincoln</LastName><ForeName>S</ForeName><Initials>S</Initials></Author><Author ValidYN="Y"><LastName>Hardy</LastName><ForeName>J</ForeName><Initials>J</Initials></Author><Author ValidYN="Y"><LastName>Amouyel</LastName><ForeName>P</ForeName><Initials>P</Initials></Author><Author ValidYN="Y"><LastName>Chartier-Harlin</LastName><ForeName>M C</ForeName><Initials>MC</Initials></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>AG17216</GrantID><Acronym>AG</Acronym><Agency>NIA NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType><PublicationType UI="D013487">Research Support, U.S. Gov't, P.H.S.</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>UNITED STATES</Country><MedlineTA>Mov Disord</MedlineTA><NlmUniqueID>8610688</NlmUniqueID><ISSNLinking>0885-3185</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D009419">Nerve Tissue Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C497604">SNCA protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D051843">Synucleins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D051844">alpha-Synuclein</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D016875">tau Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 3.1.2.-</RegistryNumber><NameOfSubstance UI="D013869">Thiolester Hydrolases</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 3.1.2.15</RegistryNumber><NameOfSubstance UI="D043222">Ubiquitin Thiolesterase</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 6.-</RegistryNumber><NameOfSubstance UI="D008025">Ligases</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 6.3.2.19</RegistryNumber><NameOfSubstance UI="D044767">Ubiquitin-Protein Ligases</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><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="D000368">Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D002886">Chromosomes, Human, Pair 17</DescriptorName><QualifierName MajorTopicYN="Y" UI="Q000235">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D002889">Chromosomes, Human, Pair 2</DescriptorName><QualifierName MajorTopicYN="Y" UI="Q000235">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D002894">Chromosomes, Human, Pair 4</DescriptorName><QualifierName MajorTopicYN="Y" UI="Q000235">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D002896">Chromosomes, Human, Pair 6</DescriptorName><QualifierName MajorTopicYN="Y" UI="Q000235">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D016000">Cluster Analysis</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D005260">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" Type="Geographic" UI="D005602">France</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="Y" UI="D008040">Genetic Linkage</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D006239">Haplotypes</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D006801">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D008025">Ligases</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 Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="Y" UI="D009154">Mutation</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D009419">Nerve Tissue Proteins</DescriptorName><QualifierName MajorTopicYN="Y" UI="Q000235">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D010300">Parkinson Disease</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000175">diagnosis</QualifierName><QualifierName MajorTopicYN="Y" UI="Q000235">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D010375">Pedigree</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D017678">Sex Distribution</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D051843">Synucleins</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D013869">Thiolester Hydrolases</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000235">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D043222">Ubiquitin Thiolesterase</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D044767">Ubiquitin-Protein Ligases</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D051844">alpha-Synuclein</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D016875">tau Proteins</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000235">genetics</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2000</Year><Month>12</Month><Day>5</Day><Hour>11</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2001</Year><Month>6</Month><Day>2</Day><Hour>10</Hour><Minute>1</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2000</Year><Month>12</Month><Day>5</Day><Hour>11</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">11104189</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>États-Unis</li></country><region><li>Floride</li></region></list><tree><noCountry><name sortKey="Amouyel, P" sort="Amouyel, P" uniqKey="Amouyel P" first="P" last="Amouyel">P. Amouyel</name><name sortKey="Becquet, E" sort="Becquet, E" uniqKey="Becquet E" first="E" last="Becquet">E. Becquet</name><name sortKey="Chartier Harlin, M C" sort="Chartier Harlin, M C" uniqKey="Chartier Harlin M" first="M C" last="Chartier-Harlin">M C Chartier-Harlin</name><name sortKey="Defebvre, L" sort="Defebvre, L" uniqKey="Defebvre L" first="L" last="Defebvre">L. Defebvre</name><name sortKey="Destee, T" sort="Destee, T" uniqKey="Destee T" first="T" last="Destée">T. Destée</name><name sortKey="Hardy, J" sort="Hardy, J" uniqKey="Hardy J" first="J" last="Hardy">J. Hardy</name><name sortKey="Lincoln, S" sort="Lincoln, S" uniqKey="Lincoln S" first="S" last="Lincoln">S. Lincoln</name><name sortKey="Mouroux, V" sort="Mouroux, V" uniqKey="Mouroux V" first="V" last="Mouroux">V. Mouroux</name><name sortKey="Richard, F" sort="Richard, F" uniqKey="Richard F" first="F" last="Richard">F. Richard</name><name sortKey="Wavrant De Vrieze, F" sort="Wavrant De Vrieze, F" uniqKey="Wavrant De Vrieze F" first="F" last="Wavrant-De Vrièze">F. Wavrant-De Vrièze</name></noCountry><country name="États-Unis"><region name="Floride"><name sortKey="Farrer, M" sort="Farrer, M" uniqKey="Farrer M" first="M" last="Farrer">M. Farrer</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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