Multiplex ligation‐dependent probe amplification assay for simultaneous detection of Parkinson's disease gene rearrangements
Identifieur interne : 001D45 ( Istex/Corpus ); précédent : 001D44; suivant : 001D46Multiplex ligation‐dependent probe amplification assay for simultaneous detection of Parkinson's disease gene rearrangements
Auteurs : Oronzo Scarciolla ; Francesco Brancati ; Enza Maria Valente ; Alessandro Ferraris ; Maria Vittoria De Angelis ; Stefano Valbonesi ; Barbara Garavaglia ; Antonino Uncini ; Giandomenico Palka ; Liborio Stuppia ; Bruno DallapiccolaSource :
- Movement Disorders [ 0885-3185 ] ; 2007-11-15.
English descriptors
Abstract
Parkinson's disease (PD) is a common disorder caused by degeneration of dopaminergic neurons in the substantia nigra and other brain areas. Mutations in several genes have been associated with both autosomal dominant PD and recessive early onset Parkinsonism (EOP). Genomic rearrangements such as deletions or multiplications of one or more exons represent a common mutational mechanism for most of these genes and are not detectable with routine mutation screening techniques. MLPA (Multiplex Ligation‐dependent Probe Amplification), is a cheap, simple, rapid, and sensitive tool to detect exon dosage alterations and specific point mutations in selected genes. We tested the recently developed PD‐MLPA assay by using 13 positive control samples carrying known mutations in SNCA, LRRK2, Parkin, PINK1, and DJ‐1 genes. We then applied this technique to screen 16 EOP patients who were then cross‐tested by quantitative PCR (qPCR). All the mutations present in the positive control samples were clearly detected by MLPA. Moreover, three novel Parkin rearrangements were identified among EOP patients and confirmed by qPCR. Only two samples generated false positive duplications of LRRK2 exon 1 and UCH‐L1 exon 9, respectively. These results show that PD‐MLPA assay can simultaneously and effectively detect rearrangements in most PD genes (SNCA, Parkin, PINK1, and DJ‐1) as well as the LRRK2 G2019S common mutation. Thus, the use of this novel platform can improve the analysis of such mutations, facilitating comprehensive genetic testing in PD and EOP. © 2007 Movement Disorder Society
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DOI: 10.1002/mds.21532
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ISTEX:942C58D5A57940D9B72ED98953BD2851C4892263Le document en format XML
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Italy</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Human Motor Sciences, University G. d'Annunzio, Chieti, Italy</mods:affiliation></affiliation></author><author><name sortKey="Valbonesi, Stefano" sort="Valbonesi, Stefano" uniqKey="Valbonesi S" first="Stefano" last="Valbonesi">Stefano Valbonesi</name><affiliation><mods:affiliation>Aging Research Center, CeSi, University G. d'Annunzio, Chieti, Italy</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Biomedical Sciences, University G. d'Annunzio, Chieti, Italy</mods:affiliation></affiliation></author><author><name sortKey="Garavaglia, Barbara" sort="Garavaglia, Barbara" uniqKey="Garavaglia B" first="Barbara" last="Garavaglia">Barbara Garavaglia</name><affiliation><mods:affiliation>Molecular Neurogenetics Unit, Foundation IRCCS Neurological Institute “C. Besta”, Milan, Italy</mods:affiliation></affiliation></author><author><name sortKey="Uncini, Antonino" sort="Uncini, Antonino" uniqKey="Uncini A" first="Antonino" last="Uncini">Antonino Uncini</name><affiliation><mods:affiliation>Neurodegenerative Diseases Unit, Aging Research Center, CeSi, University G. d'Annunzio, Chieti, Italy</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Human Motor Sciences, University G. d'Annunzio, Chieti, Italy</mods:affiliation></affiliation></author><author><name sortKey="Palka, Giandomenico" sort="Palka, Giandomenico" uniqKey="Palka G" first="Giandomenico" last="Palka">Giandomenico Palka</name><affiliation><mods:affiliation>Aging Research Center, CeSi, University G. d'Annunzio, Chieti, Italy</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Biomedical Sciences, University G. d'Annunzio, Chieti, Italy</mods:affiliation></affiliation><affiliation><mods:affiliation>Human Genetics Division, Hospital of Pescara, Pescara, Italy</mods:affiliation></affiliation></author><author><name sortKey="Stuppia, Liborio" sort="Stuppia, Liborio" uniqKey="Stuppia L" first="Liborio" last="Stuppia">Liborio Stuppia</name><affiliation><mods:affiliation>Aging Research Center, CeSi, University G. d'Annunzio, Chieti, Italy</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Biomedical Sciences, University G. d'Annunzio, Chieti, Italy</mods:affiliation></affiliation><affiliation><mods:affiliation>IGM CNR, Bologna, Italy</mods:affiliation></affiliation></author><author><name sortKey="Dallapiccola, Bruno" sort="Dallapiccola, Bruno" uniqKey="Dallapiccola B" first="Bruno" last="Dallapiccola">Bruno Dallapiccola</name><affiliation><mods:affiliation>IRCCS CSS‐Mendel Institute, Rome, Italy</mods:affiliation></affiliation><affiliation><mods:affiliation>Operative Unit of Pediatric Genetics and Immunology, Department of Medical and Surgical Pediatric Sciences, University of Messina, Messina, Italy</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Movement Disorders</title><title level="j" type="sub">Official Journal of the Movement Disorder Society</title><title level="j" type="abbrev">Mov. Disord.</title><idno type="ISSN">0885-3185</idno><idno type="eISSN">1531-8257</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2007-11-15">2007-11-15</date><biblScope unit="vol">22</biblScope><biblScope unit="issue">15</biblScope><biblScope unit="page" from="2274">2274</biblScope><biblScope unit="page" to="2278">2278</biblScope></imprint><idno type="ISSN">0885-3185</idno></series><idno type="istex">942C58D5A57940D9B72ED98953BD2851C4892263</idno><idno type="DOI">10.1002/mds.21532</idno><idno type="ArticleID">MDS21532</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0885-3185</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>MLPA</term><term>Parkinson's disease</term><term>early onset parkinsonism</term><term>genomic rearrangements</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Parkinson's disease (PD) is a common disorder caused by degeneration of dopaminergic neurons in the substantia nigra and other brain areas. Mutations in several genes have been associated with both autosomal dominant PD and recessive early onset Parkinsonism (EOP). Genomic rearrangements such as deletions or multiplications of one or more exons represent a common mutational mechanism for most of these genes and are not detectable with routine mutation screening techniques. MLPA (Multiplex Ligation‐dependent Probe Amplification), is a cheap, simple, rapid, and sensitive tool to detect exon dosage alterations and specific point mutations in selected genes. We tested the recently developed PD‐MLPA assay by using 13 positive control samples carrying known mutations in SNCA, LRRK2, Parkin, PINK1, and DJ‐1 genes. We then applied this technique to screen 16 EOP patients who were then cross‐tested by quantitative PCR (qPCR). All the mutations present in the positive control samples were clearly detected by MLPA. Moreover, three novel Parkin rearrangements were identified among EOP patients and confirmed by qPCR. Only two samples generated false positive duplications of LRRK2 exon 1 and UCH‐L1 exon 9, respectively. These results show that PD‐MLPA assay can simultaneously and effectively detect rearrangements in most PD genes (SNCA, Parkin, PINK1, and DJ‐1) as well as the LRRK2 G2019S common mutation. Thus, the use of this novel platform can improve the analysis of such mutations, facilitating comprehensive genetic testing in PD and EOP. © 2007 Movement Disorder Society</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Oronzo Scarciolla MD</name><affiliations><json:string>Aging Research Center, CeSi, University G. d'Annunzio, Chieti, Italy</json:string><json:string>Department of Biomedical Sciences, University G. d'Annunzio, Chieti, Italy</json:string><json:string>Department of Clinical Sciences and Bioimaging, University G. d'Annunzio, Chieti‐Pescara, Italy</json:string></affiliations></json:item><json:item><name>Francesco Brancati MD</name><affiliations><json:string>Aging Research Center, CeSi, University G. d'Annunzio, Chieti, Italy</json:string><json:string>Department of Biomedical Sciences, University G. d'Annunzio, Chieti, Italy</json:string><json:string>IRCCS CSS‐Mendel Institute, Rome, Italy</json:string></affiliations></json:item><json:item><name>Enza Maria Valente MD, PhD</name><affiliations><json:string>IRCCS CSS‐Mendel Institute, Rome, Italy</json:string><json:string>Operative Unit of Pediatric Genetics and Immunology, Department of Medical and Surgical Pediatric Sciences, University of Messina, Messina, Italy</json:string></affiliations></json:item><json:item><name>Alessandro Ferraris MD</name><affiliations><json:string>IRCCS CSS‐Mendel Institute, Rome, Italy</json:string><json:string>Department of Experimental Medicine and Pathology, University La Sapienza, Rome, Italy</json:string></affiliations></json:item><json:item><name>Maria Vittoria De Angelis MD</name><affiliations><json:string>Neurodegenerative Diseases Unit, Aging Research Center, CeSi, University G. d'Annunzio, Chieti, Italy</json:string><json:string>Department of Human Motor Sciences, University G. d'Annunzio, Chieti, Italy</json:string></affiliations></json:item><json:item><name>Stefano Valbonesi BPh</name><affiliations><json:string>Aging Research Center, CeSi, University G. d'Annunzio, Chieti, Italy</json:string><json:string>Department of Biomedical Sciences, University G. d'Annunzio, Chieti, Italy</json:string></affiliations></json:item><json:item><name>Barbara Garavaglia PhD</name><affiliations><json:string>Molecular Neurogenetics Unit, Foundation IRCCS Neurological Institute “C. Besta”, Milan, Italy</json:string></affiliations></json:item><json:item><name>Antonino Uncini MD</name><affiliations><json:string>Neurodegenerative Diseases Unit, Aging Research Center, CeSi, University G. d'Annunzio, Chieti, Italy</json:string><json:string>Department of Human Motor Sciences, University G. d'Annunzio, Chieti, Italy</json:string></affiliations></json:item><json:item><name>Giandomenico Palka MD</name><affiliations><json:string>Aging Research Center, CeSi, University G. d'Annunzio, Chieti, Italy</json:string><json:string>Department of Biomedical Sciences, University G. d'Annunzio, Chieti, Italy</json:string><json:string>Human Genetics Division, Hospital of Pescara, Pescara, Italy</json:string></affiliations></json:item><json:item><name>Liborio Stuppia MD</name><affiliations><json:string>Aging Research Center, CeSi, University G. d'Annunzio, Chieti, Italy</json:string><json:string>Department of Biomedical Sciences, University G. d'Annunzio, Chieti, Italy</json:string><json:string>IGM CNR, Bologna, Italy</json:string></affiliations></json:item><json:item><name>Bruno Dallapiccola MD</name><affiliations><json:string>IRCCS CSS‐Mendel Institute, Rome, Italy</json:string><json:string>Operative Unit of Pediatric Genetics and Immunology, Department of Medical and Surgical Pediatric Sciences, University of Messina, Messina, Italy</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>Parkinson's disease</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>early onset parkinsonism</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>genomic rearrangements</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>MLPA</value></json:item></subject><language><json:string>eng</json:string></language><abstract>Parkinson's disease (PD) is a common disorder caused by degeneration of dopaminergic neurons in the substantia nigra and other brain areas. Mutations in several genes have been associated with both autosomal dominant PD and recessive early onset Parkinsonism (EOP). Genomic rearrangements such as deletions or multiplications of one or more exons represent a common mutational mechanism for most of these genes and are not detectable with routine mutation screening techniques. MLPA (Multiplex Ligation‐dependent Probe Amplification), is a cheap, simple, rapid, and sensitive tool to detect exon dosage alterations and specific point mutations in selected genes. We tested the recently developed PD‐MLPA assay by using 13 positive control samples carrying known mutations in SNCA, LRRK2, Parkin, PINK1, and DJ‐1 genes. We then applied this technique to screen 16 EOP patients who were then cross‐tested by quantitative PCR (qPCR). All the mutations present in the positive control samples were clearly detected by MLPA. Moreover, three novel Parkin rearrangements were identified among EOP patients and confirmed by qPCR. Only two samples generated false positive duplications of LRRK2 exon 1 and UCH‐L1 exon 9, respectively. These results show that PD‐MLPA assay can simultaneously and effectively detect rearrangements in most PD genes (SNCA, Parkin, PINK1, and DJ‐1) as well as the LRRK2 G2019S common mutation. Thus, the use of this novel platform can improve the analysis of such mutations, facilitating comprehensive genetic testing in PD and EOP. © 2007 Movement Disorder Society</abstract><qualityIndicators><score>5.528</score><pdfVersion>1.3</pdfVersion><pdfPageSize>594 x 792 pts</pdfPageSize><refBibsNative>true</refBibsNative><abstractCharCount>1586</abstractCharCount><pdfWordCount>2684</pdfWordCount><pdfCharCount>17376</pdfCharCount><pdfPageCount>5</pdfPageCount><abstractWordCount>237</abstractWordCount></qualityIndicators><title>Multiplex ligation‐dependent probe amplification assay for simultaneous detection of Parkinson's disease gene rearrangements</title><genre><json:string>Serial article</json:string></genre><host><volume>22</volume><pages><total>5</total><last>2278</last><first>2274</first></pages><issn><json:string>0885-3185</json:string></issn><issue>15</issue><subject><json:item><value>Brief Report</value></json:item></subject><genre></genre><language><json:string>unknown</json:string></language><title>Movement Disorders</title><doi><json:string>10.1002/(ISSN)1531-8257</json:string></doi></host><publicationDate>2007</publicationDate><copyrightDate>2007</copyrightDate><doi><json:string>10.1002/mds.21532</json:string></doi><id>942C58D5A57940D9B72ED98953BD2851C4892263</id><fulltext><json:item><original>true</original><mimetype>application/pdf</mimetype><extension>pdf</extension><uri>https://api.istex.fr/document/942C58D5A57940D9B72ED98953BD2851C4892263/fulltext/pdf</uri></json:item><json:item><original>false</original><mimetype>application/zip</mimetype><extension>zip</extension><uri>https://api.istex.fr/document/942C58D5A57940D9B72ED98953BD2851C4892263/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/942C58D5A57940D9B72ED98953BD2851C4892263/fulltext/tei"><teiHeader type="text"><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Multiplex ligation‐dependent probe amplification assay for simultaneous detection of Parkinson's disease gene rearrangements</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><availability><p>Wiley Subscription Services, Inc., A Wiley Company</p></availability><date>2007</date></publicationStmt><notesStmt><note>Italian Ministry of Health (Ricerca Corrente 2006, Ricerca Finalizzata 2004 ex art. 56 to BD) - No. Telethon Grant n. GGP04291;</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Multiplex ligation‐dependent probe amplification assay for simultaneous detection of Parkinson's disease gene rearrangements</title><author><persName><forename type="first">Oronzo</forename><surname>Scarciolla</surname><roleName type="degree">MD</roleName></persName><affiliation>Aging Research Center, CeSi, University G. d'Annunzio, Chieti, Italy</affiliation><affiliation>Department of Biomedical Sciences, University G. d'Annunzio, Chieti, Italy</affiliation><affiliation>Department of Clinical Sciences and Bioimaging, University G. d'Annunzio, Chieti‐Pescara, Italy</affiliation></author><author><persName><forename type="first">Francesco</forename><surname>Brancati</surname><roleName type="degree">MD</roleName></persName><affiliation>Aging Research Center, CeSi, University G. d'Annunzio, Chieti, Italy</affiliation><affiliation>Department of Biomedical Sciences, University G. d'Annunzio, Chieti, Italy</affiliation><affiliation>IRCCS CSS‐Mendel Institute, Rome, Italy</affiliation></author><author><persName><forename type="first">Enza Maria</forename><surname>Valente</surname><roleName type="degree">MD, PhD</roleName></persName><affiliation>IRCCS CSS‐Mendel Institute, Rome, Italy</affiliation><affiliation>Operative Unit of Pediatric Genetics and Immunology, Department of Medical and Surgical Pediatric Sciences, University of Messina, Messina, Italy</affiliation></author><author><persName><forename type="first">Alessandro</forename><surname>Ferraris</surname><roleName type="degree">MD</roleName></persName><affiliation>IRCCS CSS‐Mendel Institute, Rome, Italy</affiliation><affiliation>Department of Experimental Medicine and Pathology, University La Sapienza, Rome, Italy</affiliation></author><author><persName><forename type="first">Maria Vittoria</forename><surname>De Angelis</surname><roleName type="degree">MD</roleName></persName><affiliation>Neurodegenerative Diseases Unit, Aging Research Center, CeSi, University G. d'Annunzio, Chieti, Italy</affiliation><affiliation>Department of Human Motor Sciences, University G. d'Annunzio, Chieti, Italy</affiliation></author><author><persName><forename type="first">Stefano</forename><surname>Valbonesi</surname><roleName type="degree">BPh</roleName></persName><affiliation>Aging Research Center, CeSi, University G. d'Annunzio, Chieti, Italy</affiliation><affiliation>Department of Biomedical Sciences, University G. d'Annunzio, Chieti, Italy</affiliation></author><author><persName><forename type="first">Barbara</forename><surname>Garavaglia</surname><roleName type="degree">PhD</roleName></persName><affiliation>Molecular Neurogenetics Unit, Foundation IRCCS Neurological Institute “C. Besta”, Milan, Italy</affiliation></author><author><persName><forename type="first">Antonino</forename><surname>Uncini</surname><roleName type="degree">MD</roleName></persName><affiliation>Neurodegenerative Diseases Unit, Aging Research Center, CeSi, University G. d'Annunzio, Chieti, Italy</affiliation><affiliation>Department of Human Motor Sciences, University G. d'Annunzio, Chieti, Italy</affiliation></author><author><persName><forename type="first">Giandomenico</forename><surname>Palka</surname><roleName type="degree">MD</roleName></persName><affiliation>Aging Research Center, CeSi, University G. d'Annunzio, Chieti, Italy</affiliation><affiliation>Department of Biomedical Sciences, University G. d'Annunzio, Chieti, Italy</affiliation><affiliation>Human Genetics Division, Hospital of Pescara, Pescara, Italy</affiliation></author><author><persName><forename type="first">Liborio</forename><surname>Stuppia</surname><roleName type="degree">MD</roleName></persName><note type="correspondence"><p>Correspondence: Department of Biomedical Sciences, University Gabriele d'Annunzio, Via dei Vestini, 31, 66013 Chieti, Italy</p></note><affiliation>Aging Research Center, CeSi, University G. d'Annunzio, Chieti, Italy</affiliation><affiliation>Department of Biomedical Sciences, University G. d'Annunzio, Chieti, Italy</affiliation><affiliation>IGM CNR, Bologna, Italy</affiliation></author><author><persName><forename type="first">Bruno</forename><surname>Dallapiccola</surname><roleName type="degree">MD</roleName></persName><affiliation>IRCCS CSS‐Mendel Institute, Rome, Italy</affiliation><affiliation>Operative Unit of Pediatric Genetics and Immunology, Department of Medical and Surgical Pediatric Sciences, University of Messina, Messina, Italy</affiliation></author></analytic><monogr><title level="j">Movement Disorders</title><title level="j" type="sub">Official Journal of the Movement Disorder Society</title><title level="j" type="abbrev">Mov. Disord.</title><idno type="pISSN">0885-3185</idno><idno type="eISSN">1531-8257</idno><idno type="DOI">10.1002/(ISSN)1531-8257</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2007-11-15"></date><biblScope unit="vol">22</biblScope><biblScope unit="issue">15</biblScope><biblScope unit="page" from="2274">2274</biblScope><biblScope unit="page" to="2278">2278</biblScope></imprint></monogr><idno type="istex">942C58D5A57940D9B72ED98953BD2851C4892263</idno><idno type="DOI">10.1002/mds.21532</idno><idno type="ArticleID">MDS21532</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2007</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Parkinson's disease (PD) is a common disorder caused by degeneration of dopaminergic neurons in the substantia nigra and other brain areas. Mutations in several genes have been associated with both autosomal dominant PD and recessive early onset Parkinsonism (EOP). Genomic rearrangements such as deletions or multiplications of one or more exons represent a common mutational mechanism for most of these genes and are not detectable with routine mutation screening techniques. MLPA (Multiplex Ligation‐dependent Probe Amplification), is a cheap, simple, rapid, and sensitive tool to detect exon dosage alterations and specific point mutations in selected genes. We tested the recently developed PD‐MLPA assay by using 13 positive control samples carrying known mutations in SNCA, LRRK2, Parkin, PINK1, and DJ‐1 genes. We then applied this technique to screen 16 EOP patients who were then cross‐tested by quantitative PCR (qPCR). All the mutations present in the positive control samples were clearly detected by MLPA. Moreover, three novel Parkin rearrangements were identified among EOP patients and confirmed by qPCR. Only two samples generated false positive duplications of LRRK2 exon 1 and UCH‐L1 exon 9, respectively. These results show that PD‐MLPA assay can simultaneously and effectively detect rearrangements in most PD genes (SNCA, Parkin, PINK1, and DJ‐1) as well as the LRRK2 G2019S common mutation. Thus, the use of this novel platform can improve the analysis of such mutations, facilitating comprehensive genetic testing in PD and EOP. © 2007 Movement Disorder Society</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Keywords</head><item><term>Parkinson's disease</term></item><item><term>early onset parkinsonism</term></item><item><term>genomic rearrangements</term></item><item><term>MLPA</term></item></list></keywords></textClass><textClass><keywords scheme="Journal Subject"><list><head>Article category</head><item><term>Brief Report</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2006-07-11">Received</change><change when="2007-03-19">Registration</change><change when="2007-11-15">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/942C58D5A57940D9B72ED98953BD2851C4892263/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Wiley, elements deleted: body"><istex:xmlDeclaration>version="1.0" encoding="UTF-8" standalone="yes"</istex:xmlDeclaration><istex:document><component version="2.0" type="serialArticle" xml:lang="en"><header><publicationMeta level="product"><publisherInfo><publisherName>Wiley Subscription Services, Inc., A Wiley Company</publisherName><publisherLoc>Hoboken</publisherLoc></publisherInfo><doi registered="yes">10.1002/(ISSN)1531-8257</doi><issn type="print">0885-3185</issn><issn type="electronic">1531-8257</issn><idGroup><id type="product" value="MDS"></id></idGroup><titleGroup><title type="main" xml:lang="en" sort="MOVEMENT DISORDERS">Movement Disorders</title><title type="subtitle">Official Journal of the Movement Disorder Society</title><title type="short">Mov. 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GGP04291</fundingNumber></fundingInfo><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><p>Parkinson's disease (PD) is a common disorder caused by degeneration of dopaminergic neurons in the substantia nigra and other brain areas. Mutations in several genes have been associated with both autosomal dominant PD and recessive early onset Parkinsonism (EOP). Genomic rearrangements such as deletions or multiplications of one or more exons represent a common mutational mechanism for most of these genes and are not detectable with routine mutation screening techniques. MLPA (Multiplex Ligation‐dependent Probe Amplification), is a cheap, simple, rapid, and sensitive tool to detect exon dosage alterations and specific point mutations in selected genes. We tested the recently developed PD‐MLPA assay by using 13 positive control samples carrying known mutations in <i>SNCA</i>, <i>LRRK2, Parkin, PINK1</i>, and <i>DJ</i>‐<i>1</i> genes. We then applied this technique to screen 16 EOP patients who were then cross‐tested by quantitative PCR (qPCR). All the mutations present in the positive control samples were clearly detected by MLPA. Moreover, three novel <i>Parkin</i> rearrangements were identified among EOP patients and confirmed by qPCR. Only two samples generated false positive duplications of LRRK2 exon 1 and UCH‐L1 exon 9, respectively. These results show that PD‐MLPA assay can simultaneously and effectively detect rearrangements in most PD genes (<i>SNCA</i>, <i>Parkin</i>, <i>PINK1</i>, and <i>DJ</i>‐<i>1</i>) as well as the <i>LRRK2</i> G2019S common mutation. Thus, the use of this novel platform can improve the analysis of such mutations, facilitating comprehensive genetic testing in PD and EOP. © 2007 Movement Disorder Society</p></abstract></abstractGroup></contentMeta></header></component></istex:document></istex:metadataXml><!--Version 0.6 générée le 4-12-2015--><mods version="3.6"><titleInfo lang="en"><title>Multiplex ligation‐dependent probe amplification assay for simultaneous detection of Parkinson's disease gene rearrangements</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>MLPA Assay for Detection of PD Gene Rearrangements</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Multiplex ligation‐dependent probe amplification assay for simultaneous detection of Parkinson's disease gene rearrangements</title></titleInfo><name type="personal"><namePart type="given">Oronzo</namePart><namePart type="family">Scarciolla</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Aging Research Center, CeSi, University G. d'Annunzio, Chieti, Italy</affiliation><affiliation>Department of Biomedical Sciences, University G. d'Annunzio, Chieti, Italy</affiliation><affiliation>Department of Clinical Sciences and Bioimaging, University G. d'Annunzio, Chieti‐Pescara, Italy</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Francesco</namePart><namePart type="family">Brancati</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Aging Research Center, CeSi, University G. d'Annunzio, Chieti, Italy</affiliation><affiliation>Department of Biomedical Sciences, University G. d'Annunzio, Chieti, Italy</affiliation><affiliation>IRCCS CSS‐Mendel Institute, Rome, Italy</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Enza Maria</namePart><namePart type="family">Valente</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>IRCCS CSS‐Mendel Institute, Rome, Italy</affiliation><affiliation>Operative Unit of Pediatric Genetics and Immunology, Department of Medical and Surgical Pediatric Sciences, University of Messina, Messina, Italy</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Alessandro</namePart><namePart type="family">Ferraris</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>IRCCS CSS‐Mendel Institute, Rome, Italy</affiliation><affiliation>Department of Experimental Medicine and Pathology, University La Sapienza, Rome, Italy</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Maria Vittoria</namePart><namePart type="family">De Angelis</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Neurodegenerative Diseases Unit, Aging Research Center, CeSi, University G. d'Annunzio, Chieti, Italy</affiliation><affiliation>Department of Human Motor Sciences, University G. d'Annunzio, Chieti, Italy</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Stefano</namePart><namePart type="family">Valbonesi</namePart><namePart type="termsOfAddress">BPh</namePart><affiliation>Aging Research Center, CeSi, University G. d'Annunzio, Chieti, Italy</affiliation><affiliation>Department of Biomedical Sciences, University G. d'Annunzio, Chieti, Italy</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Barbara</namePart><namePart type="family">Garavaglia</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Molecular Neurogenetics Unit, Foundation IRCCS Neurological Institute “C. Besta”, Milan, Italy</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Antonino</namePart><namePart type="family">Uncini</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Neurodegenerative Diseases Unit, Aging Research Center, CeSi, University G. d'Annunzio, Chieti, Italy</affiliation><affiliation>Department of Human Motor Sciences, University G. d'Annunzio, Chieti, Italy</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Giandomenico</namePart><namePart type="family">Palka</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Aging Research Center, CeSi, University G. d'Annunzio, Chieti, Italy</affiliation><affiliation>Department of Biomedical Sciences, University G. d'Annunzio, Chieti, Italy</affiliation><affiliation>Human Genetics Division, Hospital of Pescara, Pescara, Italy</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Liborio</namePart><namePart type="family">Stuppia</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Aging Research Center, CeSi, University G. d'Annunzio, Chieti, Italy</affiliation><affiliation>Department of Biomedical Sciences, University G. d'Annunzio, Chieti, Italy</affiliation><affiliation>IGM CNR, Bologna, Italy</affiliation><description>Correspondence: Department of Biomedical Sciences, University Gabriele d'Annunzio, Via dei Vestini, 31, 66013 Chieti, Italy</description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Bruno</namePart><namePart type="family">Dallapiccola</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>IRCCS CSS‐Mendel Institute, Rome, Italy</affiliation><affiliation>Operative Unit of Pediatric Genetics and Immunology, Department of Medical and Surgical Pediatric Sciences, University of Messina, Messina, Italy</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre authority="originalCategForm">article</genre><originInfo><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><place><placeTerm type="text">Hoboken</placeTerm></place><dateIssued encoding="w3cdtf">2007-11-15</dateIssued><dateCaptured encoding="w3cdtf">2006-07-11</dateCaptured><dateValid encoding="w3cdtf">2007-03-19</dateValid><copyrightDate encoding="w3cdtf">2007</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType><extent unit="figures">1</extent><extent unit="tables">1</extent><extent unit="references">13</extent><extent unit="words">2717</extent></physicalDescription><abstract lang="en">Parkinson's disease (PD) is a common disorder caused by degeneration of dopaminergic neurons in the substantia nigra and other brain areas. Mutations in several genes have been associated with both autosomal dominant PD and recessive early onset Parkinsonism (EOP). Genomic rearrangements such as deletions or multiplications of one or more exons represent a common mutational mechanism for most of these genes and are not detectable with routine mutation screening techniques. MLPA (Multiplex Ligation‐dependent Probe Amplification), is a cheap, simple, rapid, and sensitive tool to detect exon dosage alterations and specific point mutations in selected genes. We tested the recently developed PD‐MLPA assay by using 13 positive control samples carrying known mutations in SNCA, LRRK2, Parkin, PINK1, and DJ‐1 genes. We then applied this technique to screen 16 EOP patients who were then cross‐tested by quantitative PCR (qPCR). All the mutations present in the positive control samples were clearly detected by MLPA. Moreover, three novel Parkin rearrangements were identified among EOP patients and confirmed by qPCR. Only two samples generated false positive duplications of LRRK2 exon 1 and UCH‐L1 exon 9, respectively. These results show that PD‐MLPA assay can simultaneously and effectively detect rearrangements in most PD genes (SNCA, Parkin, PINK1, and DJ‐1) as well as the LRRK2 G2019S common mutation. Thus, the use of this novel platform can improve the analysis of such mutations, facilitating comprehensive genetic testing in PD and EOP. © 2007 Movement Disorder Society</abstract><note type="funding">Italian Ministry of Health (Ricerca Corrente 2006, Ricerca Finalizzata 2004 ex art. 56 to BD) - No. Telethon Grant n. GGP04291; </note><subject lang="en"><genre>Keywords</genre><topic>Parkinson's disease</topic><topic>early onset parkinsonism</topic><topic>genomic rearrangements</topic><topic>MLPA</topic></subject><relatedItem type="host"><titleInfo><title>Movement Disorders</title><subTitle>Official Journal of the Movement Disorder Society</subTitle></titleInfo><titleInfo type="abbreviated"><title>Mov. Disord.</title></titleInfo><subject><genre>article category</genre><topic>Brief Report</topic></subject><identifier type="ISSN">0885-3185</identifier><identifier type="eISSN">1531-8257</identifier><identifier type="DOI">10.1002/(ISSN)1531-8257</identifier><identifier type="PublisherID">MDS</identifier><part><date>2007</date><detail type="volume"><caption>vol.</caption><number>22</number></detail><detail type="issue"><caption>no.</caption><number>15</number></detail><extent unit="pages"><start>2274</start><end>2278</end><total>5</total></extent></part></relatedItem><identifier type="istex">942C58D5A57940D9B72ED98953BD2851C4892263</identifier><identifier type="DOI">10.1002/mds.21532</identifier><identifier type="ArticleID">MDS21532</identifier><accessCondition type="use and reproduction" contentType="copyright">Copyright © 2007 Movement Disorder Society</accessCondition><recordInfo><recordOrigin>Wiley Subscription Services, Inc., A Wiley Company</recordOrigin><recordContentSource>WILEY</recordContentSource></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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