PINK1 mutations in sporadic early-onset Parkinson's disease.
Identifieur interne : 001576 ( Ncbi/Merge ); précédent : 001575; suivant : 001577PINK1 mutations in sporadic early-onset Parkinson's disease.
Auteurs : Eng-King Tan [Singapour] ; Kenneth Yew ; Eva Chua ; K. Puvan ; Hui Shen ; Esther Lee ; Kim-Yoong Puong ; Yi Zhao ; Ratnagopal Pavanni ; Meng-Cheong Wong ; Dominic Jamora ; Deidre De Silva ; Kyaw-Thu Moe ; Fung-Peng Woon ; Yih Yuen ; Louis TanSource :
- Movement disorders : official journal of the Movement Disorder Society [ 0885-3185 ] ; 2006.
Descripteurs français
- Wicri :
- geographic : Singapour.
English descriptors
- KwdEn :
- MESH :
- chemical , genetics : Protein Kinases.
- chemical : DNA Primers.
- geographic : Singapore.
- genetics : Asian Continental Ancestry Group, Parkinson Disease.
- Adult, Age of Onset, Base Sequence, Ethnic Groups, Heterozygote Detection, Homozygote, Humans, Middle Aged, Mutation.
Abstract
Pathogenic PINK1 mutations have been described in PARK6-linked Parkinson's disease (PD) patients of Asian origin. However, data on the frequency of PINK1 mutations in sporadic early-onset Parkinson's disease (EOPD) Asian patients are lacking. The objectives of this study were to report the frequency of PINK1 mutations of sporadic EOPD in an Asian cohort comprising of ethnic Chinese, Malays, and Indians, and to highlight a PINK1-positive patient who presented with restless legs symptoms. Eighty consecutive sporadic EOPD patients from the movement disorder clinics of two major tertiary institutions in the country were included. We performed sequence analysis of all the coding and exon-intron junctions of the PINK1 using specific primer sets. In addition, we genotyped polymorphisms detected from the analysis in a group of sporadic PD patients and controls. Three different mutations (two homozygous nonsense and one heterozygous missense) in the putative kinase domain were found in three patients, giving a 3.7% frequency of PINK1 mutations in our EOPD cohort. All the mutations were absent in 200 healthy controls. One patient with a novel homozygous nonsense PINK1 mutation presented unusually with restless legs symptoms. Separately, analysis of the frequency of four PINK1 polymorphisms in a group of sporadic PD and controls did not reveal any significant differences. We highlight a 3.7% frequency of PINK1 mutations in an Asian cohort (ethnic Chinese, Malay, and Indian) of EOPD. The phenotypic spectrum associated with PINK1-positive patients may be wider than previously reported. Polymorphisms of PINK1 do not appear to modulate risk of PD in our population.
DOI: 10.1002/mds.20810
PubMed: 16482571
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">PINK1 mutations in sporadic early-onset Parkinson's disease.</title><author><name sortKey="Tan, Eng King" sort="Tan, Eng King" uniqKey="Tan E" first="Eng-King" last="Tan">Eng-King Tan</name><affiliation wicri:level="1"><nlm:affiliation>Division of Research, SingHealth, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Division of Research, SingHealth</wicri:regionArea><wicri:noRegion>SingHealth</wicri:noRegion></affiliation></author><author><name sortKey="Yew, Kenneth" sort="Yew, Kenneth" uniqKey="Yew K" first="Kenneth" last="Yew">Kenneth Yew</name></author><author><name sortKey="Chua, Eva" sort="Chua, Eva" uniqKey="Chua E" first="Eva" last="Chua">Eva Chua</name></author><author><name sortKey="Puvan, K" sort="Puvan, K" uniqKey="Puvan K" first="K" last="Puvan">K. Puvan</name></author><author><name sortKey="Shen, Hui" sort="Shen, Hui" uniqKey="Shen H" first="Hui" last="Shen">Hui Shen</name></author><author><name sortKey="Lee, Esther" sort="Lee, Esther" uniqKey="Lee E" first="Esther" last="Lee">Esther Lee</name></author><author><name sortKey="Puong, Kim Yoong" sort="Puong, Kim Yoong" uniqKey="Puong K" first="Kim-Yoong" last="Puong">Kim-Yoong Puong</name></author><author><name sortKey="Zhao, Yi" sort="Zhao, Yi" uniqKey="Zhao Y" first="Yi" last="Zhao">Yi Zhao</name></author><author><name sortKey="Pavanni, Ratnagopal" sort="Pavanni, Ratnagopal" uniqKey="Pavanni R" first="Ratnagopal" last="Pavanni">Ratnagopal Pavanni</name></author><author><name sortKey="Wong, Meng Cheong" sort="Wong, Meng Cheong" uniqKey="Wong M" first="Meng-Cheong" last="Wong">Meng-Cheong Wong</name></author><author><name sortKey="Jamora, Dominic" sort="Jamora, Dominic" uniqKey="Jamora D" first="Dominic" last="Jamora">Dominic Jamora</name></author><author><name sortKey="De Silva, Deidre" sort="De Silva, Deidre" uniqKey="De Silva D" first="Deidre" last="De Silva">Deidre De Silva</name></author><author><name sortKey="Moe, Kyaw Thu" sort="Moe, Kyaw Thu" uniqKey="Moe K" first="Kyaw-Thu" last="Moe">Kyaw-Thu Moe</name></author><author><name sortKey="Woon, Fung Peng" sort="Woon, Fung Peng" uniqKey="Woon F" first="Fung-Peng" last="Woon">Fung-Peng Woon</name></author><author><name sortKey="Yuen, Yih" sort="Yuen, Yih" uniqKey="Yuen Y" first="Yih" last="Yuen">Yih Yuen</name></author><author><name sortKey="Tan, Louis" sort="Tan, Louis" uniqKey="Tan L" first="Louis" last="Tan">Louis Tan</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2006">2006</date><idno type="doi">10.1002/mds.20810</idno><idno type="RBID">pubmed:16482571</idno><idno type="pmid">16482571</idno><idno type="wicri:Area/PubMed/Corpus">002D55</idno><idno type="wicri:Area/PubMed/Curation">002D55</idno><idno type="wicri:Area/PubMed/Checkpoint">002B89</idno><idno type="wicri:Area/Ncbi/Merge">001576</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">PINK1 mutations in sporadic early-onset Parkinson's disease.</title><author><name sortKey="Tan, Eng King" sort="Tan, Eng King" uniqKey="Tan E" first="Eng-King" last="Tan">Eng-King Tan</name><affiliation wicri:level="1"><nlm:affiliation>Division of Research, SingHealth, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Division of Research, SingHealth</wicri:regionArea><wicri:noRegion>SingHealth</wicri:noRegion></affiliation></author><author><name sortKey="Yew, Kenneth" sort="Yew, Kenneth" uniqKey="Yew K" first="Kenneth" last="Yew">Kenneth Yew</name></author><author><name sortKey="Chua, Eva" sort="Chua, Eva" uniqKey="Chua E" first="Eva" last="Chua">Eva Chua</name></author><author><name sortKey="Puvan, K" sort="Puvan, K" uniqKey="Puvan K" first="K" last="Puvan">K. Puvan</name></author><author><name sortKey="Shen, Hui" sort="Shen, Hui" uniqKey="Shen H" first="Hui" last="Shen">Hui Shen</name></author><author><name sortKey="Lee, Esther" sort="Lee, Esther" uniqKey="Lee E" first="Esther" last="Lee">Esther Lee</name></author><author><name sortKey="Puong, Kim Yoong" sort="Puong, Kim Yoong" uniqKey="Puong K" first="Kim-Yoong" last="Puong">Kim-Yoong Puong</name></author><author><name sortKey="Zhao, Yi" sort="Zhao, Yi" uniqKey="Zhao Y" first="Yi" last="Zhao">Yi Zhao</name></author><author><name sortKey="Pavanni, Ratnagopal" sort="Pavanni, Ratnagopal" uniqKey="Pavanni R" first="Ratnagopal" last="Pavanni">Ratnagopal Pavanni</name></author><author><name sortKey="Wong, Meng Cheong" sort="Wong, Meng Cheong" uniqKey="Wong M" first="Meng-Cheong" last="Wong">Meng-Cheong Wong</name></author><author><name sortKey="Jamora, Dominic" sort="Jamora, Dominic" uniqKey="Jamora D" first="Dominic" last="Jamora">Dominic Jamora</name></author><author><name sortKey="De Silva, Deidre" sort="De Silva, Deidre" uniqKey="De Silva D" first="Deidre" last="De Silva">Deidre De Silva</name></author><author><name sortKey="Moe, Kyaw Thu" sort="Moe, Kyaw Thu" uniqKey="Moe K" first="Kyaw-Thu" last="Moe">Kyaw-Thu Moe</name></author><author><name sortKey="Woon, Fung Peng" sort="Woon, Fung Peng" uniqKey="Woon F" first="Fung-Peng" last="Woon">Fung-Peng Woon</name></author><author><name sortKey="Yuen, Yih" sort="Yuen, Yih" uniqKey="Yuen Y" first="Yih" last="Yuen">Yih Yuen</name></author><author><name sortKey="Tan, Louis" sort="Tan, Louis" uniqKey="Tan L" first="Louis" last="Tan">Louis Tan</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="2006" type="published">2006</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term><term>Age of Onset</term><term>Asian Continental Ancestry Group (genetics)</term><term>Base Sequence</term><term>DNA Primers</term><term>Ethnic Groups</term><term>Heterozygote Detection</term><term>Homozygote</term><term>Humans</term><term>Middle Aged</term><term>Mutation</term><term>Parkinson Disease (genetics)</term><term>Protein Kinases (genetics)</term><term>Singapore</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Protein Kinases</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>DNA Primers</term></keywords><keywords scheme="MESH" type="geographic" xml:lang="en"><term>Singapore</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Asian Continental Ancestry Group</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adult</term><term>Age of Onset</term><term>Base Sequence</term><term>Ethnic Groups</term><term>Heterozygote Detection</term><term>Homozygote</term><term>Humans</term><term>Middle Aged</term><term>Mutation</term></keywords><keywords scheme="Wicri" type="geographic" xml:lang="fr"><term>Singapour</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Pathogenic PINK1 mutations have been described in PARK6-linked Parkinson's disease (PD) patients of Asian origin. However, data on the frequency of PINK1 mutations in sporadic early-onset Parkinson's disease (EOPD) Asian patients are lacking. The objectives of this study were to report the frequency of PINK1 mutations of sporadic EOPD in an Asian cohort comprising of ethnic Chinese, Malays, and Indians, and to highlight a PINK1-positive patient who presented with restless legs symptoms. Eighty consecutive sporadic EOPD patients from the movement disorder clinics of two major tertiary institutions in the country were included. We performed sequence analysis of all the coding and exon-intron junctions of the PINK1 using specific primer sets. In addition, we genotyped polymorphisms detected from the analysis in a group of sporadic PD patients and controls. Three different mutations (two homozygous nonsense and one heterozygous missense) in the putative kinase domain were found in three patients, giving a 3.7% frequency of PINK1 mutations in our EOPD cohort. All the mutations were absent in 200 healthy controls. One patient with a novel homozygous nonsense PINK1 mutation presented unusually with restless legs symptoms. Separately, analysis of the frequency of four PINK1 polymorphisms in a group of sporadic PD and controls did not reveal any significant differences. We highlight a 3.7% frequency of PINK1 mutations in an Asian cohort (ethnic Chinese, Malay, and Indian) of EOPD. The phenotypic spectrum associated with PINK1-positive patients may be wider than previously reported. Polymorphisms of PINK1 do not appear to modulate risk of PD in our population.</div></front></TEI><pubmed><MedlineCitation Owner="NLM" Status="MEDLINE"><PMID Version="1">16482571</PMID><DateCreated><Year>2006</Year><Month>06</Month><Day>13</Day></DateCreated><DateCompleted><Year>2006</Year><Month>11</Month><Day>14</Day></DateCompleted><DateRevised><Year>2012</Year><Month>06</Month><Day>19</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0885-3185</ISSN><JournalIssue CitedMedium="Print"><Volume>21</Volume><Issue>6</Issue><PubDate><Year>2006</Year><Month>Jun</Month></PubDate></JournalIssue><Title>Movement disorders : official journal of the Movement Disorder Society</Title><ISOAbbreviation>Mov. Disord.</ISOAbbreviation></Journal><ArticleTitle>PINK1 mutations in sporadic early-onset Parkinson's disease.</ArticleTitle><Pagination><MedlinePgn>789-93</MedlinePgn></Pagination><Abstract><AbstractText>Pathogenic PINK1 mutations have been described in PARK6-linked Parkinson's disease (PD) patients of Asian origin. However, data on the frequency of PINK1 mutations in sporadic early-onset Parkinson's disease (EOPD) Asian patients are lacking. The objectives of this study were to report the frequency of PINK1 mutations of sporadic EOPD in an Asian cohort comprising of ethnic Chinese, Malays, and Indians, and to highlight a PINK1-positive patient who presented with restless legs symptoms. Eighty consecutive sporadic EOPD patients from the movement disorder clinics of two major tertiary institutions in the country were included. We performed sequence analysis of all the coding and exon-intron junctions of the PINK1 using specific primer sets. In addition, we genotyped polymorphisms detected from the analysis in a group of sporadic PD patients and controls. Three different mutations (two homozygous nonsense and one heterozygous missense) in the putative kinase domain were found in three patients, giving a 3.7% frequency of PINK1 mutations in our EOPD cohort. All the mutations were absent in 200 healthy controls. One patient with a novel homozygous nonsense PINK1 mutation presented unusually with restless legs symptoms. Separately, analysis of the frequency of four PINK1 polymorphisms in a group of sporadic PD and controls did not reveal any significant differences. We highlight a 3.7% frequency of PINK1 mutations in an Asian cohort (ethnic Chinese, Malay, and Indian) of EOPD. The phenotypic spectrum associated with PINK1-positive patients may be wider than previously reported. Polymorphisms of PINK1 do not appear to modulate risk of PD in our population.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Tan</LastName><ForeName>Eng-King</ForeName><Initials>EK</Initials><AffiliationInfo><Affiliation>Division of Research, SingHealth, Singapore.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yew</LastName><ForeName>Kenneth</ForeName><Initials>K</Initials></Author><Author ValidYN="Y"><LastName>Chua</LastName><ForeName>Eva</ForeName><Initials>E</Initials></Author><Author ValidYN="Y"><LastName>Puvan</LastName><ForeName>K</ForeName><Initials>K</Initials></Author><Author ValidYN="Y"><LastName>Shen</LastName><ForeName>Hui</ForeName><Initials>H</Initials></Author><Author ValidYN="Y"><LastName>Lee</LastName><ForeName>Esther</ForeName><Initials>E</Initials></Author><Author ValidYN="Y"><LastName>Puong</LastName><ForeName>Kim-Yoong</ForeName><Initials>KY</Initials></Author><Author ValidYN="Y"><LastName>Zhao</LastName><ForeName>Yi</ForeName><Initials>Y</Initials></Author><Author ValidYN="Y"><LastName>Pavanni</LastName><ForeName>Ratnagopal</ForeName><Initials>R</Initials></Author><Author ValidYN="Y"><LastName>Wong</LastName><ForeName>Meng-Cheong</ForeName><Initials>MC</Initials></Author><Author ValidYN="Y"><LastName>Jamora</LastName><ForeName>Dominic</ForeName><Initials>D</Initials></Author><Author ValidYN="Y"><LastName>de Silva</LastName><ForeName>Deidre</ForeName><Initials>D</Initials></Author><Author ValidYN="Y"><LastName>Moe</LastName><ForeName>Kyaw-Thu</ForeName><Initials>KT</Initials></Author><Author ValidYN="Y"><LastName>Woon</LastName><ForeName>Fung-Peng</ForeName><Initials>FP</Initials></Author><Author ValidYN="Y"><LastName>Yuen</LastName><ForeName>Yih</ForeName><Initials>Y</Initials></Author><Author ValidYN="Y"><LastName>Tan</LastName><ForeName>Louis</ForeName><Initials>L</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D002363">Case Reports</PublicationType><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 Disord</MedlineTA><NlmUniqueID>8610688</NlmUniqueID><ISSNLinking>0885-3185</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D017931">DNA Primers</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="C433927">PTEN-induced putative kinase</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="D044466">Asian Continental Ancestry Group</DescriptorName><QualifierName MajorTopicYN="Y" UI="Q000235">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D001483">Base Sequence</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D017931">DNA Primers</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D005006">Ethnic Groups</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D006580">Heterozygote Detection</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D006720">Homozygote</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D006801">Humans</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="D010300">Parkinson Disease</DescriptorName><QualifierName MajorTopicYN="Y" UI="Q000235">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D011494">Protein Kinases</DescriptorName><QualifierName MajorTopicYN="Y" UI="Q000235">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" Type="Geographic" UI="D012846">Singapore</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2006</Year><Month>2</Month><Day>17</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2006</Year><Month>11</Month><Day>15</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2006</Year><Month>2</Month><Day>17</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="doi">10.1002/mds.20810</ArticleId><ArticleId IdType="pubmed">16482571</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Singapour</li></country></list><tree><noCountry><name sortKey="Chua, Eva" sort="Chua, Eva" uniqKey="Chua E" first="Eva" last="Chua">Eva Chua</name><name sortKey="De Silva, Deidre" sort="De Silva, Deidre" uniqKey="De Silva D" first="Deidre" last="De Silva">Deidre De Silva</name><name sortKey="Jamora, Dominic" sort="Jamora, Dominic" uniqKey="Jamora D" first="Dominic" last="Jamora">Dominic Jamora</name><name sortKey="Lee, Esther" sort="Lee, Esther" uniqKey="Lee E" first="Esther" last="Lee">Esther Lee</name><name sortKey="Moe, Kyaw Thu" sort="Moe, Kyaw Thu" uniqKey="Moe K" first="Kyaw-Thu" last="Moe">Kyaw-Thu Moe</name><name sortKey="Pavanni, Ratnagopal" sort="Pavanni, Ratnagopal" uniqKey="Pavanni R" first="Ratnagopal" last="Pavanni">Ratnagopal Pavanni</name><name sortKey="Puong, Kim Yoong" sort="Puong, Kim Yoong" uniqKey="Puong K" first="Kim-Yoong" last="Puong">Kim-Yoong Puong</name><name sortKey="Puvan, K" sort="Puvan, K" uniqKey="Puvan K" first="K" last="Puvan">K. Puvan</name><name sortKey="Shen, Hui" sort="Shen, Hui" uniqKey="Shen H" first="Hui" last="Shen">Hui Shen</name><name sortKey="Tan, Louis" sort="Tan, Louis" uniqKey="Tan L" first="Louis" last="Tan">Louis Tan</name><name sortKey="Wong, Meng Cheong" sort="Wong, Meng Cheong" uniqKey="Wong M" first="Meng-Cheong" last="Wong">Meng-Cheong Wong</name><name sortKey="Woon, Fung Peng" sort="Woon, Fung Peng" uniqKey="Woon F" first="Fung-Peng" last="Woon">Fung-Peng Woon</name><name sortKey="Yew, Kenneth" sort="Yew, Kenneth" uniqKey="Yew K" first="Kenneth" last="Yew">Kenneth Yew</name><name sortKey="Yuen, Yih" sort="Yuen, Yih" uniqKey="Yuen Y" first="Yih" last="Yuen">Yih Yuen</name><name sortKey="Zhao, Yi" sort="Zhao, Yi" uniqKey="Zhao Y" first="Yi" last="Zhao">Yi Zhao</name></noCountry><country name="Singapour"><noRegion><name sortKey="Tan, Eng King" sort="Tan, Eng King" uniqKey="Tan E" first="Eng-King" last="Tan">Eng-King Tan</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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