Genetic screening reveals high frequency of PARK2 mutations and reduced Parkin expression conferring risk for Parkinsonism in North West India
Identifieur interne : 000728 ( Main/Corpus ); précédent : 000727; suivant : 000729Genetic screening reveals high frequency of PARK2 mutations and reduced Parkin expression conferring risk for Parkinsonism in North West India
Auteurs : Monika Vinish ; Sudesh Prabhakar ; Madhu Khullar ; Indu Verma ; Akshay AnandSource :
- Journal of Neurology, Neurosurgery & Psychiatry [ 0022-3050 ] ; 2010-02.
Abstract
Background Among several aetiological factors, PARK2 mutations are the most common cause of Parkinson disease (PD) that result in degeneration of dopaminergic neurons in the substantia nigra. Methods In order to examine the contribution of PARK2 mutations and corresponding Parkin expression in blood of North West Indian PD patients, the authors screened 120 000 patients from 2001 to 2006 for features of PD using UK Parkinson disease society brain bank clinical diagnostic criteria (UKPDBBC), and tested PARK2 mutations in 69 of those that fulfilled this criteria. 43 controls lacking extrapyramidal signs were also analysed. Results The PCR analysis revealed the occurrence of homozygous deletions in 28 of 69 samples analysed (40.5%) represented by exon-1 (15.9%), exon-3 (11.5%), and exon-12 (11.5%). Sequencing revealed point mutations in exon 4 and exon 9 in six of these patients (8.7%) including one novel missense Gly1083Trp mutation in one patient. Parkin estimation was done by combination of immunolocalisation and FACS analysis revealing reduced Parkin expression among PD patients. The mutations in exons 1, 3 and 12 among sporadic PD patients were found to be higher among younger onset variants (age<45 years). This report also constitutes the first evidence that PARK 2 mutations contribute to the aberration in Parkin expression in blood leading to PD.
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DOI: 10.1136/jnnp.2008.157255
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Khullar</name><affiliation><mods:affiliation>Department of Experimental Medicine and Biotechnology, Post Graduate Institute of Medical Education and Research, Chandigarh, India</mods:affiliation></affiliation></author><author><name sortKey="Verma, Indu" sort="Verma, Indu" uniqKey="Verma I" first="Indu" last="Verma">Indu Verma</name><affiliation><mods:affiliation>Department of Biochemistry, Post Graduate Institute of Medical Education and Research, Chandigarh, India</mods:affiliation></affiliation></author><author><name sortKey="Anand, Akshay" sort="Anand, Akshay" uniqKey="Anand A" first="Akshay" last="Anand">Akshay Anand</name><affiliation><mods:affiliation>Department of Neurology, Post Graduate Institute of Medical Education and Research, Chandigarh, India</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: akshay1anand@rediffmail.com</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno 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Prabhakar</name><affiliation><mods:affiliation>Department of Neurology, Post Graduate Institute of Medical Education and Research, Chandigarh, India</mods:affiliation></affiliation></author><author><name sortKey="Khullar, Madhu" sort="Khullar, Madhu" uniqKey="Khullar M" first="Madhu" last="Khullar">Madhu Khullar</name><affiliation><mods:affiliation>Department of Experimental Medicine and Biotechnology, Post Graduate Institute of Medical Education and Research, Chandigarh, India</mods:affiliation></affiliation></author><author><name sortKey="Verma, Indu" sort="Verma, Indu" uniqKey="Verma I" first="Indu" last="Verma">Indu Verma</name><affiliation><mods:affiliation>Department of Biochemistry, Post Graduate Institute of Medical Education and Research, Chandigarh, India</mods:affiliation></affiliation></author><author><name sortKey="Anand, Akshay" sort="Anand, Akshay" uniqKey="Anand A" first="Akshay" last="Anand">Akshay Anand</name><affiliation><mods:affiliation>Department of Neurology, Post Graduate Institute of Medical Education and Research, Chandigarh, India</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: akshay1anand@rediffmail.com</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Journal of Neurology, Neurosurgery & Psychiatry</title><title level="j" type="abbrev">J Neurol Neurosurg Psychiatry</title><idno type="ISSN">0022-3050</idno><idno type="eISSN">1468-330X</idno><imprint><publisher>BMJ Publishing Group Ltd</publisher><date type="published" when="2010-02">2010-02</date><biblScope unit="volume">81</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="166">166</biblScope></imprint><idno type="ISSN">0022-3050</idno></series><idno type="istex">81376F1272EC0BC09F706EF23FA90B01AA96422D</idno><idno type="DOI">10.1136/jnnp.2008.157255</idno><idno type="href">jnnp-81-166.pdf</idno><idno type="ArticleID">jnnp157255</idno><idno type="PMID">19734163</idno><idno type="Related-article-Href">10.1136/jnnp.2008.162834</idno><idno type="related-article-ID">RA1</idno><idno type="local">jnnp;81/2/166</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0022-3050</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract">Background Among several aetiological factors, PARK2 mutations are the most common cause of Parkinson disease (PD) that result in degeneration of dopaminergic neurons in the substantia nigra. Methods In order to examine the contribution of PARK2 mutations and corresponding Parkin expression in blood of North West Indian PD patients, the authors screened 120 000 patients from 2001 to 2006 for features of PD using UK Parkinson disease society brain bank clinical diagnostic criteria (UKPDBBC), and tested PARK2 mutations in 69 of those that fulfilled this criteria. 43 controls lacking extrapyramidal signs were also analysed. Results The PCR analysis revealed the occurrence of homozygous deletions in 28 of 69 samples analysed (40.5%) represented by exon-1 (15.9%), exon-3 (11.5%), and exon-12 (11.5%). Sequencing revealed point mutations in exon 4 and exon 9 in six of these patients (8.7%) including one novel missense Gly1083Trp mutation in one patient. Parkin estimation was done by combination of immunolocalisation and FACS analysis revealing reduced Parkin expression among PD patients. The mutations in exons 1, 3 and 12 among sporadic PD patients were found to be higher among younger onset variants (age<45 years). This report also constitutes the first evidence that PARK 2 mutations contribute to the aberration in Parkin expression in blood leading to PD.</div></front></TEI><istex><corpusName>bmj</corpusName><author><json:item><name>Monika Vinish</name><affiliations><json:string>Department of Neurology, Post Graduate Institute of Medical Education and Research, Chandigarh, India</json:string></affiliations></json:item><json:item><name>Sudesh Prabhakar</name><affiliations><json:string>Department of Neurology, Post Graduate Institute of Medical Education and Research, Chandigarh, India</json:string></affiliations></json:item><json:item><name>Madhu Khullar</name><affiliations><json:string>Department of Experimental Medicine and Biotechnology, Post Graduate Institute of Medical Education and Research, Chandigarh, India</json:string></affiliations></json:item><json:item><name>Indu Verma</name><affiliations><json:string>Department of Biochemistry, Post Graduate Institute of Medical Education and Research, Chandigarh, India</json:string></affiliations></json:item><json:item><name>Akshay Anand</name><affiliations><json:string>Department of Neurology, Post Graduate Institute of Medical Education and Research, Chandigarh, India</json:string><json:string>E-mail: akshay1anand@rediffmail.com</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>Research paper</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Parkinson disease</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>PARK2</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>parkin expression</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>FACS</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>early onset PD</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>molecular biology</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>movement disorders</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>neuroepidemiology</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>neurogenetics</value></json:item></subject><language><json:string>eng</json:string></language><abstract>Background Among several aetiological factors, PARK2 mutations are the most common cause of Parkinson disease (PD) that result in degeneration of dopaminergic neurons in the substantia nigra. Methods In order to examine the contribution of PARK2 mutations and corresponding Parkin expression in blood of North West Indian PD patients, the authors screened 120 000 patients from 2001 to 2006 for features of PD using UK Parkinson disease society brain bank clinical diagnostic criteria (UKPDBBC), and tested PARK2 mutations in 69 of those that fulfilled this criteria. 43 controls lacking extrapyramidal signs were also analysed. Results The PCR analysis revealed the occurrence of homozygous deletions in 28 of 69 samples analysed (40.5%) represented by exon-1 (15.9%), exon-3 (11.5%), and exon-12 (11.5%). Sequencing revealed point mutations in exon 4 and exon 9 in six of these patients (8.7%) including one novel missense Gly1083Trp mutation in one patient. Parkin estimation was done by combination of immunolocalisation and FACS analysis revealing reduced Parkin expression among PD patients. The mutations in exons 1, 3 and 12 among sporadic PD patients were found to be higher among younger onset variants (age>45 years). This report also constitutes the first evidence that PARK 2 mutations contribute to the aberration in Parkin expression in blood leading to PD.</abstract><qualityIndicators><score>6.888</score><pdfVersion>1.4</pdfVersion><pdfPageSize>595.276 x 793.701 pts</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>10</keywordCount><abstractCharCount>1372</abstractCharCount><pdfWordCount>3904</pdfWordCount><pdfCharCount>26069</pdfCharCount><pdfPageCount>5</pdfPageCount><abstractWordCount>207</abstractWordCount></qualityIndicators><title>Genetic screening reveals high frequency of PARK2 mutations and reduced Parkin expression conferring risk for Parkinsonism in North West India</title><pmid><json:string>19734163</json:string></pmid><genre><json:string>research-article</json:string></genre><host><volume>81</volume><pages><first>166</first></pages><issn><json:string>0022-3050</json:string></issn><issue>2</issue><genre></genre><language><json:string>unknown</json:string></language><eissn><json:string>1468-330X</json:string></eissn><title>Journal of Neurology, Neurosurgery & Psychiatry</title></host><publicationDate>2010</publicationDate><copyrightDate>2009</copyrightDate><doi><json:string>10.1136/jnnp.2008.157255</json:string></doi><id>81376F1272EC0BC09F706EF23FA90B01AA96422D</id><fulltext><json:item><original>true</original><mimetype>application/pdf</mimetype><extension>pdf</extension><uri>https://api.istex.fr/document/81376F1272EC0BC09F706EF23FA90B01AA96422D/fulltext/pdf</uri></json:item><json:item><original>false</original><mimetype>application/zip</mimetype><extension>zip</extension><uri>https://api.istex.fr/document/81376F1272EC0BC09F706EF23FA90B01AA96422D/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/81376F1272EC0BC09F706EF23FA90B01AA96422D/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a">Genetic screening reveals high frequency of PARK2 mutations and reduced Parkin expression conferring risk for Parkinsonism in North West India</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>BMJ Publishing Group Ltd</publisher><availability><p>BMJ</p></availability><date>2009-09-03</date></publicationStmt><notesStmt><note>See Editorial Commentary, p128</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a">Genetic screening reveals high frequency of PARK2 mutations and reduced Parkin expression conferring risk for Parkinsonism in North West India</title><author><persName><forename type="first">Monika</forename><surname>Vinish</surname></persName><affiliation>Department of Neurology, Post Graduate Institute of Medical Education and Research, Chandigarh, India</affiliation></author><author><persName><forename type="first">Sudesh</forename><surname>Prabhakar</surname></persName><affiliation>Department of Neurology, Post Graduate Institute of Medical Education and Research, Chandigarh, India</affiliation></author><author><persName><forename type="first">Madhu</forename><surname>Khullar</surname></persName><affiliation>Department of Experimental Medicine and Biotechnology, Post Graduate Institute of Medical Education and Research, Chandigarh, India</affiliation></author><author><persName><forename type="first">Indu</forename><surname>Verma</surname></persName><affiliation>Department of Biochemistry, Post Graduate Institute of Medical Education and Research, Chandigarh, India</affiliation></author><author corresp="yes"><persName><forename type="first">Akshay</forename><surname>Anand</surname></persName><email>akshay1anand@rediffmail.com</email><affiliation>Department of Neurology, Post Graduate Institute of Medical Education and Research, Chandigarh, India</affiliation></author></analytic><monogr><title level="j">Journal of Neurology, Neurosurgery & Psychiatry</title><title level="j" type="abbrev">J Neurol Neurosurg Psychiatry</title><idno type="pISSN">0022-3050</idno><idno type="eISSN">1468-330X</idno><imprint><publisher>BMJ Publishing Group Ltd</publisher><date type="published" when="2010-02"></date><biblScope unit="volume">81</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="166">166</biblScope></imprint></monogr><idno type="istex">81376F1272EC0BC09F706EF23FA90B01AA96422D</idno><idno type="DOI">10.1136/jnnp.2008.157255</idno><idno type="href">jnnp-81-166.pdf</idno><idno type="ArticleID">jnnp157255</idno><idno type="PMID">19734163</idno><idno type="Related-article-Href">10.1136/jnnp.2008.162834</idno><idno type="related-article-ID">RA1</idno><idno type="local">jnnp;81/2/166</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2009-09-03</date></creation><langUsage><language ident="en">en</language></langUsage><abstract><p>Background Among several aetiological factors, PARK2 mutations are the most common cause of Parkinson disease (PD) that result in degeneration of dopaminergic neurons in the substantia nigra. Methods In order to examine the contribution of PARK2 mutations and corresponding Parkin expression in blood of North West Indian PD patients, the authors screened 120 000 patients from 2001 to 2006 for features of PD using UK Parkinson disease society brain bank clinical diagnostic criteria (UKPDBBC), and tested PARK2 mutations in 69 of those that fulfilled this criteria. 43 controls lacking extrapyramidal signs were also analysed. Results The PCR analysis revealed the occurrence of homozygous deletions in 28 of 69 samples analysed (40.5%) represented by exon-1 (15.9%), exon-3 (11.5%), and exon-12 (11.5%). Sequencing revealed point mutations in exon 4 and exon 9 in six of these patients (8.7%) including one novel missense Gly1083Trp mutation in one patient. Parkin estimation was done by combination of immunolocalisation and FACS analysis revealing reduced Parkin expression among PD patients. The mutations in exons 1, 3 and 12 among sporadic PD patients were found to be higher among younger onset variants (age<45 years). This report also constitutes the first evidence that PARK 2 mutations contribute to the aberration in Parkin expression in blood leading to PD.</p></abstract><textClass><keywords scheme="keyword"><list><head>Keywords</head><item><term>Parkinson disease</term></item><item><term>PARK2</term></item><item><term>parkin expression</term></item><item><term>FACS</term></item><item><term>early onset PD</term></item><item><term>molecular biology</term></item><item><term>movement disorders</term></item><item><term>neuroepidemiology</term></item><item><term>neurogenetics</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2009-09-03">Created</change><change when="2010-02">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/81376F1272EC0BC09F706EF23FA90B01AA96422D/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="corpus bmj" wicri:toSee="no header"><istex:xmlDeclaration>version="1.0" encoding="UTF-8" standalone="no"</istex:xmlDeclaration><istex:docType PUBLIC="-//NLM//DTD Journal Archiving and Interchange DTD v2.3 20070202//EN" URI="archivearticle.dtd" name="istex:docType"></istex:docType><istex:document><article article-type="research-article"><front><journal-meta><journal-id journal-id-type="hwp">jnnp</journal-id><journal-id journal-id-type="nlm-ta">J Neurol Neurosurg Psychiatry</journal-id><journal-id journal-id-type="publisher-id">JNNP</journal-id><journal-title>Journal of Neurology, Neurosurgery & Psychiatry</journal-title><abbrev-journal-title abbrev-type="publisher">J Neurol Neurosurg Psychiatry</abbrev-journal-title><abbrev-journal-title>J Neurol Neurosurg Psychiatry</abbrev-journal-title><issn pub-type="ppub">0022-3050</issn><issn pub-type="epub">1468-330X</issn><publisher><publisher-name>BMJ Publishing Group Ltd</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">jnnp157255</article-id><article-id pub-id-type="doi">10.1136/jnnp.2008.157255</article-id><article-id pub-id-type="other">jnnp;81/2/166</article-id><article-id pub-id-type="other">jnnp;jnnp.2008.157255</article-id><article-id pub-id-type="pmid">19734163</article-id><article-id pub-id-type="other">166</article-id><article-id pub-id-type="other">jnnp.2008.157255</article-id><article-categories><subj-group subj-group-type="heading"><subject content-type="original">Research paper</subject></subj-group></article-categories><title-group><article-title>Genetic screening reveals high frequency of <italic>PARK2</italic> mutations and reduced <italic>Parkin</italic> expression conferring risk for Parkinsonism in North West India</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Vinish</surname><given-names>Monika</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Prabhakar</surname><given-names>Sudesh</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Khullar</surname><given-names>Madhu</given-names></name><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Verma</surname><given-names>Indu</given-names></name><xref ref-type="aff" rid="aff3">3</xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Anand</surname><given-names>Akshay</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib></contrib-group><aff id="aff1"><label>1</label>Department of Neurology, Post Graduate Institute of Medical Education and Research, Chandigarh, India</aff><aff id="aff2"><label>2</label>Department of Experimental Medicine and Biotechnology, Post Graduate Institute of Medical Education and Research, Chandigarh, India</aff><aff id="aff3"><label>3</label>Department of Biochemistry, Post Graduate Institute of Medical Education and Research, Chandigarh, India</aff><author-notes><corresp><label>Correspondence to</label> Akshay Anand, Department of Neurology, Post Graduate Institute of Medical Education and Research, Sector-12 Chandigarh 160012, India; <email>akshay1anand@rediffmail.com</email></corresp><fn fn-type="other"><p>See Editorial Commentary, <related-article id="RA1" related-article-type="in-this-issue" ext-link-type="doi" xlink:type="simple" xlink:href="10.1136/jnnp.2008.162834">p128</related-article></p></fn><fn fn-type="other"><p>MV and AA contributed equally to this paper</p></fn><fn fn-type="other"><p>Supplementary material is published online only at <ext-link ext-link-type="uri" xlink:href="http://jnnp.bmj.com/content/vol81/issue2">http://jnnp.bmj.com/content/vol81/issue2</ext-link></p></fn></author-notes><pub-date pub-type="epub-original"><day>3</day><month>9</month><year>2009</year></pub-date><pub-date pub-type="ppub"><month>2</month><year>2010</year></pub-date><pub-date pub-type="epub"><day>3</day><month>9</month><year>2009</year></pub-date><volume>81</volume><volume-id pub-id-type="other">81</volume-id><volume-id pub-id-type="other">81</volume-id><issue>2</issue><issue-id pub-id-type="other">jnnp;81/2</issue-id><issue-id pub-id-type="other">2</issue-id><issue-id pub-id-type="other">81/2</issue-id><fpage>166</fpage><history><date date-type="received"><day>6</day><month>7</month><year>2008</year></date><date date-type="rev-recd"><day>18</day><month>6</month><year>2009</year></date><date date-type="accepted"><day>5</day><month>7</month><year>2009</year></date></history><permissions><copyright-statement>© 2009, Published by the BMJ Publishing Group Limited For permission to use, (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.</copyright-statement><copyright-year>2009</copyright-year></permissions><self-uri content-type="pdf" xlink:role="full-text" xlink:href="jnnp-81-166.pdf"></self-uri><abstract><sec><title>Background</title><p>Among several aetiological factors, <italic>PARK2</italic> mutations are the most common cause of Parkinson disease (PD) that result in degeneration of dopaminergic neurons in the substantia nigra.</p></sec><sec><title>Methods</title><p>In order to examine the contribution of <italic>PARK2</italic> mutations and corresponding <italic>Parkin</italic> expression in blood of North West Indian PD patients, the authors screened 120 000 patients from 2001 to 2006 for features of PD using UK Parkinson disease society brain bank clinical diagnostic criteria (UKPDBBC), and tested <italic>PARK2</italic> mutations in 69 of those that fulfilled this criteria. 43 controls lacking extrapyramidal signs were also analysed.</p></sec><sec><title>Results</title><p>The PCR analysis revealed the occurrence of homozygous deletions in 28 of 69 samples analysed (40.5%) represented by exon-1 (15.9%), exon-3 (11.5%), and exon-12 (11.5%). Sequencing revealed point mutations in exon 4 and exon 9 in six of these patients (8.7%) including one novel missense <italic>Gly1083Trp</italic> mutation in one patient. <italic>Parkin</italic> estimation was done by combination of immunolocalisation and FACS analysis revealing reduced <italic>Parkin</italic> expression among PD patients. The mutations in exons 1, 3 and 12 among sporadic PD patients were found to be higher among younger onset variants (age<45 years). This report also constitutes the first evidence that <italic>PARK 2</italic> mutations contribute to the aberration in <italic>Parkin</italic> expression in blood leading to PD.</p></sec></abstract><kwd-group><kwd>Parkinson disease</kwd><kwd><italic>PARK2</italic></kwd><kwd><italic>parkin</italic> expression</kwd><kwd>FACS</kwd><kwd>early onset PD</kwd><kwd>molecular biology</kwd><kwd>movement disorders</kwd><kwd>neuroepidemiology</kwd><kwd>neurogenetics</kwd></kwd-group></article-meta></front></article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo><title>Genetic screening reveals high frequency of PARK2 mutations and reduced Parkin expression conferring risk for Parkinsonism in North West India</title></titleInfo><titleInfo type="alternative" contentType="CDATA"><title>Genetic screening reveals high frequency of PARK2 mutations and reduced Parkin expression conferring risk for Parkinsonism in North West India</title></titleInfo><name type="personal"><namePart type="given">Monika</namePart><namePart type="family">Vinish</namePart><affiliation>Department of Neurology, Post Graduate Institute of Medical Education and Research, Chandigarh, India</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Sudesh</namePart><namePart type="family">Prabhakar</namePart><affiliation>Department of Neurology, Post Graduate Institute of Medical Education and Research, Chandigarh, India</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Madhu</namePart><namePart type="family">Khullar</namePart><affiliation>Department of Experimental Medicine and Biotechnology, Post Graduate Institute of Medical Education and Research, Chandigarh, India</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Indu</namePart><namePart type="family">Verma</namePart><affiliation>Department of Biochemistry, Post Graduate Institute of Medical Education and Research, Chandigarh, India</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal" displayLabel="corresp"><namePart type="given">Akshay</namePart><namePart type="family">Anand</namePart><affiliation>Department of Neurology, Post Graduate Institute of Medical Education and Research, Chandigarh, India</affiliation><affiliation>E-mail: akshay1anand@rediffmail.com</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="research-article"></genre><originInfo><publisher>BMJ Publishing Group Ltd</publisher><dateIssued encoding="w3cdtf">2010-02</dateIssued><dateCreated encoding="w3cdtf">2009-09-03</dateCreated><copyrightDate encoding="w3cdtf">2009</copyrightDate></originInfo><language><languageTerm type="code" authority="iso639-2b">eng</languageTerm><languageTerm type="code" authority="rfc3066">en</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType></physicalDescription><abstract>Background Among several aetiological factors, PARK2 mutations are the most common cause of Parkinson disease (PD) that result in degeneration of dopaminergic neurons in the substantia nigra. Methods In order to examine the contribution of PARK2 mutations and corresponding Parkin expression in blood of North West Indian PD patients, the authors screened 120 000 patients from 2001 to 2006 for features of PD using UK Parkinson disease society brain bank clinical diagnostic criteria (UKPDBBC), and tested PARK2 mutations in 69 of those that fulfilled this criteria. 43 controls lacking extrapyramidal signs were also analysed. Results The PCR analysis revealed the occurrence of homozygous deletions in 28 of 69 samples analysed (40.5%) represented by exon-1 (15.9%), exon-3 (11.5%), and exon-12 (11.5%). Sequencing revealed point mutations in exon 4 and exon 9 in six of these patients (8.7%) including one novel missense Gly1083Trp mutation in one patient. Parkin estimation was done by combination of immunolocalisation and FACS analysis revealing reduced Parkin expression among PD patients. The mutations in exons 1, 3 and 12 among sporadic PD patients were found to be higher among younger onset variants (age<45 years). This report also constitutes the first evidence that PARK 2 mutations contribute to the aberration in Parkin expression in blood leading to PD.</abstract><note type="footnotes">See Editorial Commentary, p128</note><subject><genre>Keywords</genre><topic>Parkinson disease</topic><topic>PARK2</topic><topic>parkin expression</topic><topic>FACS</topic><topic>early onset PD</topic><topic>molecular biology</topic><topic>movement disorders</topic><topic>neuroepidemiology</topic><topic>neurogenetics</topic></subject><relatedItem type="host"><titleInfo><title>Journal of Neurology, Neurosurgery & Psychiatry</title></titleInfo><titleInfo type="abbreviated"><title>J Neurol Neurosurg Psychiatry</title></titleInfo><genre type="Journal">journal</genre><identifier type="ISSN">0022-3050</identifier><identifier type="eISSN">1468-330X</identifier><identifier type="PublisherID">JNNP</identifier><identifier type="PublisherID-hwp">jnnp</identifier><identifier type="PublisherID-nlm-ta">J Neurol Neurosurg Psychiatry</identifier><part><date>2010</date><detail type="volume"><caption>vol.</caption><number>81</number></detail><detail type="issue"><caption>no.</caption><number>2</number></detail><extent unit="pages"><start>166</start></extent></part></relatedItem><identifier type="istex">81376F1272EC0BC09F706EF23FA90B01AA96422D</identifier><identifier type="DOI">10.1136/jnnp.2008.157255</identifier><identifier type="href">jnnp-81-166.pdf</identifier><identifier type="ArticleID">jnnp157255</identifier><identifier type="PMID">19734163</identifier><identifier type="Related-article-Href">10.1136/jnnp.2008.162834</identifier><identifier type="related-article-ID">RA1</identifier><identifier type="local">jnnp;81/2/166</identifier><accessCondition type="use and reproduction" contentType="copyright">© 2009, Published by the BMJ Publishing Group Limited For permission to use, (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.</accessCondition><recordInfo><recordContentSource>BMJ</recordContentSource></recordInfo></mods></metadata><annexes><json:item><original>true</original><mimetype>image/jpeg</mimetype><extension>jpeg</extension><uri>https://api.istex.fr/document/81376F1272EC0BC09F706EF23FA90B01AA96422D/annexes/jpeg</uri></json:item></annexes><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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