The curious case of phenocopies in families with genetic Parkinson's disease.
Identifieur interne : 001088 ( PubMed/Curation ); précédent : 001087; suivant : 001089The curious case of phenocopies in families with genetic Parkinson's disease.
Auteurs : Christine Klein [Canada] ; Rosalind Chuang ; Connie Marras ; Anthony E. LangSource :
- Movement disorders : official journal of the Movement Disorder Society [ 1531-8257 ] ; 2011.
English descriptors
- KwdEn :
- MESH :
- chemical , genetics : Protein Kinases, Protein-Serine-Threonine Kinases, Ubiquitin-Protein Ligases, alpha-Synuclein.
- genetics : Mutation, Parkinson Disease.
- Family Health, Genetic Predisposition to Disease, Genetic Testing, Humans, Phenotype.
Abstract
Monogenic forms of Parkinson's disease account for ∼3% of all "idiopathic" Parkinson's disease. With reduced penetrance in dominant forms and manifesting heterozygotes in recessive forms of Parkinson's disease, it has been well recognized that inheritance patterns do not always follow classic Mendelian genetics. A novel twist to the puzzle is the presence of phenocopies (i.e., family members with the same clinical syndrome as the mutation carriers, but lacking the familial mutation). We reviewed all pedigrees published between 1997 and 2009 with α-synuclein, leucine-rich repeat kinase 2, Parkin, or PTEN-induced kinase 1 mutations with at least 2 affected individuals and known genetic status for the possible presence of phenocopies. Of 537 patients with clinical Parkinson's disease in 160 families meeting our inclusion criteria, 27 patients (5.0%) from 23 families (14.4%) were phenocopies. Phenocopies represented 3.8% of all blood relatives reported in the pedigrees containing phenocopies and an estimated 1.3% of all blood relatives in all pedigrees included. Both of these rates exceeded age-specific prevalences of Parkinson's disease. In 4 families, the phenocopy was explained by another known mutation: In 2 pedigrees, a monogenic cause was likely; in another 2, secondary parkinsonism was suspected; and in the remaining 15 families, "sporadic Parkinson's disease" was suggested as the cause of disease in the phenocopy. The unexpectedly high number of phenocopies of mostly unknown origin within families with a seemingly known etiology of Parkinson's disease adds another level of complexity to genetic research of Parkinson's disease, as well as to the interpretation of genetic testing results in the clinical diagnostic setting.
DOI: 10.1002/mds.23853
PubMed: 21735483
Links toward previous steps (curation, corpus...)
- to stream PubMed, to step Corpus: Pour aller vers cette notice dans l'étape Curation :001088
Links to Exploration step
pubmed:21735483Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">The curious case of phenocopies in families with genetic Parkinson's disease.</title><author><name sortKey="Klein, Christine" sort="Klein, Christine" uniqKey="Klein C" first="Christine" last="Klein">Christine Klein</name><affiliation wicri:level="1"><nlm:affiliation>Morton and Gloria Shulman Movement Disorders Center and the Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Morton and Gloria Shulman Movement Disorders Center and the Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital, University of Toronto, Toronto, Ontario</wicri:regionArea></affiliation></author><author><name sortKey="Chuang, Rosalind" sort="Chuang, Rosalind" uniqKey="Chuang R" first="Rosalind" last="Chuang">Rosalind Chuang</name></author><author><name sortKey="Marras, Connie" sort="Marras, Connie" uniqKey="Marras C" first="Connie" last="Marras">Connie Marras</name></author><author><name sortKey="Lang, Anthony E" sort="Lang, Anthony E" uniqKey="Lang A" first="Anthony E" last="Lang">Anthony E. Lang</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2011">2011</date><idno type="doi">10.1002/mds.23853</idno><idno type="RBID">pubmed:21735483</idno><idno type="pmid">21735483</idno><idno type="wicri:Area/PubMed/Corpus">001088</idno><idno type="wicri:Area/PubMed/Curation">001088</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">The curious case of phenocopies in families with genetic Parkinson's disease.</title><author><name sortKey="Klein, Christine" sort="Klein, Christine" uniqKey="Klein C" first="Christine" last="Klein">Christine Klein</name><affiliation wicri:level="1"><nlm:affiliation>Morton and Gloria Shulman Movement Disorders Center and the Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Morton and Gloria Shulman Movement Disorders Center and the Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital, University of Toronto, Toronto, Ontario</wicri:regionArea></affiliation></author><author><name sortKey="Chuang, Rosalind" sort="Chuang, Rosalind" uniqKey="Chuang R" first="Rosalind" last="Chuang">Rosalind Chuang</name></author><author><name sortKey="Marras, Connie" sort="Marras, Connie" uniqKey="Marras C" first="Connie" last="Marras">Connie Marras</name></author><author><name sortKey="Lang, Anthony E" sort="Lang, Anthony E" uniqKey="Lang A" first="Anthony E" last="Lang">Anthony E. Lang</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="2011" type="published">2011</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Family Health</term><term>Genetic Predisposition to Disease</term><term>Genetic Testing</term><term>Humans</term><term>Mutation (genetics)</term><term>Parkinson Disease (genetics)</term><term>Phenotype</term><term>Protein Kinases (genetics)</term><term>Protein-Serine-Threonine Kinases (genetics)</term><term>Ubiquitin-Protein Ligases (genetics)</term><term>alpha-Synuclein (genetics)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Protein Kinases</term><term>Protein-Serine-Threonine Kinases</term><term>Ubiquitin-Protein Ligases</term><term>alpha-Synuclein</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Mutation</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Family Health</term><term>Genetic Predisposition to Disease</term><term>Genetic Testing</term><term>Humans</term><term>Phenotype</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Monogenic forms of Parkinson's disease account for ∼3% of all "idiopathic" Parkinson's disease. With reduced penetrance in dominant forms and manifesting heterozygotes in recessive forms of Parkinson's disease, it has been well recognized that inheritance patterns do not always follow classic Mendelian genetics. A novel twist to the puzzle is the presence of phenocopies (i.e., family members with the same clinical syndrome as the mutation carriers, but lacking the familial mutation). We reviewed all pedigrees published between 1997 and 2009 with α-synuclein, leucine-rich repeat kinase 2, Parkin, or PTEN-induced kinase 1 mutations with at least 2 affected individuals and known genetic status for the possible presence of phenocopies. Of 537 patients with clinical Parkinson's disease in 160 families meeting our inclusion criteria, 27 patients (5.0%) from 23 families (14.4%) were phenocopies. Phenocopies represented 3.8% of all blood relatives reported in the pedigrees containing phenocopies and an estimated 1.3% of all blood relatives in all pedigrees included. Both of these rates exceeded age-specific prevalences of Parkinson's disease. In 4 families, the phenocopy was explained by another known mutation: In 2 pedigrees, a monogenic cause was likely; in another 2, secondary parkinsonism was suspected; and in the remaining 15 families, "sporadic Parkinson's disease" was suggested as the cause of disease in the phenocopy. The unexpectedly high number of phenocopies of mostly unknown origin within families with a seemingly known etiology of Parkinson's disease adds another level of complexity to genetic research of Parkinson's disease, as well as to the interpretation of genetic testing results in the clinical diagnostic setting.</div></front></TEI><pubmed><MedlineCitation Owner="NLM" Status="MEDLINE"><PMID Version="1">21735483</PMID><DateCreated><Year>2011</Year><Month>12</Month><Day>16</Day></DateCreated><DateCompleted><Year>2012</Year><Month>04</Month><Day>23</Day></DateCompleted><DateRevised><Year>2012</Year><Month>06</Month><Day>25</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1531-8257</ISSN><JournalIssue CitedMedium="Internet"><Volume>26</Volume><Issue>10</Issue><PubDate><Year>2011</Year><Month>Aug</Month><Day>15</Day></PubDate></JournalIssue><Title>Movement disorders : official journal of the Movement Disorder Society</Title><ISOAbbreviation>Mov. Disord.</ISOAbbreviation></Journal><ArticleTitle>The curious case of phenocopies in families with genetic Parkinson's disease.</ArticleTitle><Pagination><MedlinePgn>1793-802</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1002/mds.23853</ELocationID><Abstract><AbstractText>Monogenic forms of Parkinson's disease account for ∼3% of all "idiopathic" Parkinson's disease. With reduced penetrance in dominant forms and manifesting heterozygotes in recessive forms of Parkinson's disease, it has been well recognized that inheritance patterns do not always follow classic Mendelian genetics. A novel twist to the puzzle is the presence of phenocopies (i.e., family members with the same clinical syndrome as the mutation carriers, but lacking the familial mutation). We reviewed all pedigrees published between 1997 and 2009 with α-synuclein, leucine-rich repeat kinase 2, Parkin, or PTEN-induced kinase 1 mutations with at least 2 affected individuals and known genetic status for the possible presence of phenocopies. Of 537 patients with clinical Parkinson's disease in 160 families meeting our inclusion criteria, 27 patients (5.0%) from 23 families (14.4%) were phenocopies. Phenocopies represented 3.8% of all blood relatives reported in the pedigrees containing phenocopies and an estimated 1.3% of all blood relatives in all pedigrees included. Both of these rates exceeded age-specific prevalences of Parkinson's disease. In 4 families, the phenocopy was explained by another known mutation: In 2 pedigrees, a monogenic cause was likely; in another 2, secondary parkinsonism was suspected; and in the remaining 15 families, "sporadic Parkinson's disease" was suggested as the cause of disease in the phenocopy. The unexpectedly high number of phenocopies of mostly unknown origin within families with a seemingly known etiology of Parkinson's disease adds another level of complexity to genetic research of Parkinson's disease, as well as to the interpretation of genetic testing results in the clinical diagnostic setting.</AbstractText><CopyrightInformation>Copyright © 2011 Movement Disorder Society.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Klein</LastName><ForeName>Christine</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Morton and Gloria Shulman Movement Disorders Center and the Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chuang</LastName><ForeName>Rosalind</ForeName><Initials>R</Initials></Author><Author ValidYN="Y"><LastName>Marras</LastName><ForeName>Connie</ForeName><Initials>C</Initials></Author><Author ValidYN="Y"><LastName>Lang</LastName><ForeName>Anthony E</ForeName><Initials>AE</Initials></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><Agency>Canadian Institutes of Health Research</Agency><Country>Canada</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType><PublicationType UI="D016454">Review</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2011</Year><Month>07</Month><Day>06</Day></ArticleDate></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="D051844">alpha-Synuclein</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.-</RegistryNumber><NameOfSubstance UI="D011494">Protein Kinases</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.11.1</RegistryNumber><NameOfSubstance UI="C495280">LRRK2 protein, 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="Y" UI="D005192">Family Health</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="Y" UI="D020022">Genetic Predisposition to Disease</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D005820">Genetic Testing</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D006801">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D009154">Mutation</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000235">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D010300">Parkinson Disease</DescriptorName><QualifierName MajorTopicYN="Y" 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="D044767">Ubiquitin-Protein Ligases</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000235">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D051844">alpha-Synuclein</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000235">genetics</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2011</Year><Month>3</Month><Day>21</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2011</Year><Month>5</Month><Day>11</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2011</Year><Month>5</Month><Day>26</Day></PubMedPubDate><PubMedPubDate PubStatus="aheadofprint"><Year>2011</Year><Month>7</Month><Day>6</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2011</Year><Month>7</Month><Day>8</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2011</Year><Month>7</Month><Day>8</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2012</Year><Month>4</Month><Day>24</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="doi">10.1002/mds.23853</ArticleId><ArticleId IdType="pubmed">21735483</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Santé/explor/MovDisordV3/Data/PubMed/Curation
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001088 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/PubMed/Curation/biblio.hfd -nk 001088 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Santé
|area= MovDisordV3
|flux= PubMed
|étape= Curation
|type= RBID
|clé= pubmed:21735483
|texte= The curious case of phenocopies in families with genetic Parkinson's disease.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/PubMed/Curation/RBID.i -Sk "pubmed:21735483" \
| HfdSelect -Kh $EXPLOR_AREA/Data/PubMed/Curation/biblio.hfd \
| NlmPubMed2Wicri -a MovDisordV3
| This area was generated with Dilib version V0.6.23. |  |