Novel parkin mutations detected in patients with early-onset Parkinson's disease
A multiethnic series of patients with early‐onset Parkinson's disease (EOP) was studied to assess the frequency and nature of parkin/PARK2 gene mutations and to investigate phenotype–genotype relationships. Forty‐six EOP probands with an onset age of G, and exon 8‐9‐10 deletion. Homozygous muta...
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| Veröffentlicht in: | Movement disorders 2005-04, Vol.20 (4), p.424-431 |
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| creator | Bertoli-Avella, Aida M. Giroud-Benitez, José L. Akyol, Ali Barbosa, Egberto Schaap, Onno van der Linde, Herma C. Martignoni, Emilia Lopiano, Leonardo Lamberti, Paolo Fincati, Emiliana Antonini, Angelo Stocchi, Fabrizio Montagna, Pasquale Squitieri, Ferdinando Marini, Paolo Abbruzzese, Giovanni Fabbrini, Giovanni Marconi, Roberto Dalla Libera, Alessio Trianni, Giorgio Guidi, Marco De Gaetano, Antonio Boff Maegawa, Gustavo De Leo, Antonino Gallai, Virgilio de Rosa, Giulia Vanacore, Nicola Meco, Giuseppe van Duijn, Cornelia M. Oostra, Ben A. Heutink, Peter Bonifati, Vincenzo |
| description | A multiethnic series of patients with early‐onset Parkinson's disease (EOP) was studied to assess the frequency and nature of parkin/PARK2 gene mutations and to investigate phenotype–genotype relationships. Forty‐six EOP probands with an onset age of G, and exon 8‐9‐10 deletion. Homozygous mutations, two heterozygous mutations, and a single heterozygous mutation were found in 8, 6, and 1 patient, respectively. Heterozygous exon deletions represented 28% of the mutant alleles. The patients with parkin mutations showed significantly earlier onset, longer disease duration, more frequently symmetric onset, and slower disease progression than the patients without mutations, in agreement with previous studies. This study confirms the frequent involvement of parkin and the importance of genetic testing in the diagnostic work‐up of EOP. © 2004 Movement Disorder Society |
| doi_str_mv | 10.1002/mds.20343 |
| format | Article |
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Forty‐six EOP probands with an onset age of <45 years, and 14 affected relatives were ascertained from Italy, Brazil, Cuba, and Turkey. The genetic screening included direct sequencing and exon dosage using a new, cost‐effective, real‐time polymerase chain reaction method. Mutations were found in 33% of the indexes overall, and in 53% of those with family history compatible with autosomal recessive inheritance. Fifteen parkin alterations (10 exon deletions and five point mutations) were identified, including four novel mutations: Arg402Cys, Cys418Arg, IVS11‐3C>G, and exon 8‐9‐10 deletion. Homozygous mutations, two heterozygous mutations, and a single heterozygous mutation were found in 8, 6, and 1 patient, respectively. Heterozygous exon deletions represented 28% of the mutant alleles. The patients with parkin mutations showed significantly earlier onset, longer disease duration, more frequently symmetric onset, and slower disease progression than the patients without mutations, in agreement with previous studies. This study confirms the frequent involvement of parkin and the importance of genetic testing in the diagnostic work‐up of EOP. © 2004 Movement Disorder Society</description><identifier>ISSN: 0885-3185</identifier><identifier>EISSN: 1531-8257</identifier><identifier>DOI: 10.1002/mds.20343</identifier><identifier>PMID: 15584030</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Adolescent ; Adult ; Age of Onset ; Aged ; Biological and medical sciences ; Cost-Benefit Analysis ; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases ; early-onset ; Exons - genetics ; Female ; gene dosage ; Gene Library ; Genotype ; Humans ; Intracellular Signaling Peptides and Proteins ; Male ; Mass Screening - methods ; Medical sciences ; Middle Aged ; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis ; mutation ; Neurology ; Oncogene Proteins - genetics ; parkin ; Parkinson Disease - economics ; Parkinson Disease - epidemiology ; Parkinson Disease - genetics ; Parkinson's disease ; Phenotype ; Point Mutation - genetics ; Polymerase Chain Reaction ; Protein Deglycase DJ-1 ; Protein Kinases - genetics ; Ubiquitin-Protein Ligases - genetics</subject><ispartof>Movement disorders, 2005-04, Vol.20 (4), p.424-431</ispartof><rights>Copyright © 2004 Movement Disorder Society</rights><rights>2005 INIST-CNRS</rights><rights>Copyright 2004 Movement Disorder Society.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4223-97a39d157ba6d70ec4a62f26509c6315d6177273974bb91550bd5065a25908f13</citedby><cites>FETCH-LOGICAL-c4223-97a39d157ba6d70ec4a62f26509c6315d6177273974bb91550bd5065a25908f13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fmds.20343$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fmds.20343$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16801518$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15584030$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bertoli-Avella, Aida M.</creatorcontrib><creatorcontrib>Giroud-Benitez, José L.</creatorcontrib><creatorcontrib>Akyol, Ali</creatorcontrib><creatorcontrib>Barbosa, Egberto</creatorcontrib><creatorcontrib>Schaap, Onno</creatorcontrib><creatorcontrib>van der Linde, Herma C.</creatorcontrib><creatorcontrib>Martignoni, Emilia</creatorcontrib><creatorcontrib>Lopiano, Leonardo</creatorcontrib><creatorcontrib>Lamberti, Paolo</creatorcontrib><creatorcontrib>Fincati, Emiliana</creatorcontrib><creatorcontrib>Antonini, Angelo</creatorcontrib><creatorcontrib>Stocchi, Fabrizio</creatorcontrib><creatorcontrib>Montagna, Pasquale</creatorcontrib><creatorcontrib>Squitieri, Ferdinando</creatorcontrib><creatorcontrib>Marini, Paolo</creatorcontrib><creatorcontrib>Abbruzzese, Giovanni</creatorcontrib><creatorcontrib>Fabbrini, Giovanni</creatorcontrib><creatorcontrib>Marconi, Roberto</creatorcontrib><creatorcontrib>Dalla Libera, Alessio</creatorcontrib><creatorcontrib>Trianni, Giorgio</creatorcontrib><creatorcontrib>Guidi, Marco</creatorcontrib><creatorcontrib>De Gaetano, Antonio</creatorcontrib><creatorcontrib>Boff Maegawa, Gustavo</creatorcontrib><creatorcontrib>De Leo, Antonino</creatorcontrib><creatorcontrib>Gallai, Virgilio</creatorcontrib><creatorcontrib>de Rosa, Giulia</creatorcontrib><creatorcontrib>Vanacore, Nicola</creatorcontrib><creatorcontrib>Meco, Giuseppe</creatorcontrib><creatorcontrib>van Duijn, Cornelia M.</creatorcontrib><creatorcontrib>Oostra, Ben A.</creatorcontrib><creatorcontrib>Heutink, Peter</creatorcontrib><creatorcontrib>Bonifati, Vincenzo</creatorcontrib><creatorcontrib>Italian Parkinson Genetics Network, MD</creatorcontrib><creatorcontrib>The Italian Parkinson Genetics Network, MD</creatorcontrib><title>Novel parkin mutations detected in patients with early-onset Parkinson's disease</title><title>Movement disorders</title><addtitle>Mov. Disord</addtitle><description>A multiethnic series of patients with early‐onset Parkinson's disease (EOP) was studied to assess the frequency and nature of parkin/PARK2 gene mutations and to investigate phenotype–genotype relationships. Forty‐six EOP probands with an onset age of <45 years, and 14 affected relatives were ascertained from Italy, Brazil, Cuba, and Turkey. The genetic screening included direct sequencing and exon dosage using a new, cost‐effective, real‐time polymerase chain reaction method. Mutations were found in 33% of the indexes overall, and in 53% of those with family history compatible with autosomal recessive inheritance. Fifteen parkin alterations (10 exon deletions and five point mutations) were identified, including four novel mutations: Arg402Cys, Cys418Arg, IVS11‐3C>G, and exon 8‐9‐10 deletion. Homozygous mutations, two heterozygous mutations, and a single heterozygous mutation were found in 8, 6, and 1 patient, respectively. Heterozygous exon deletions represented 28% of the mutant alleles. The patients with parkin mutations showed significantly earlier onset, longer disease duration, more frequently symmetric onset, and slower disease progression than the patients without mutations, in agreement with previous studies. This study confirms the frequent involvement of parkin and the importance of genetic testing in the diagnostic work‐up of EOP. © 2004 Movement Disorder Society</description><subject>Adolescent</subject><subject>Adult</subject><subject>Age of Onset</subject><subject>Aged</subject><subject>Biological and medical sciences</subject><subject>Cost-Benefit Analysis</subject><subject>Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases</subject><subject>early-onset</subject><subject>Exons - genetics</subject><subject>Female</subject><subject>gene dosage</subject><subject>Gene Library</subject><subject>Genotype</subject><subject>Humans</subject><subject>Intracellular Signaling Peptides and Proteins</subject><subject>Male</subject><subject>Mass Screening - methods</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis</subject><subject>mutation</subject><subject>Neurology</subject><subject>Oncogene Proteins - genetics</subject><subject>parkin</subject><subject>Parkinson Disease - economics</subject><subject>Parkinson Disease - epidemiology</subject><subject>Parkinson Disease - genetics</subject><subject>Parkinson's disease</subject><subject>Phenotype</subject><subject>Point Mutation - genetics</subject><subject>Polymerase Chain Reaction</subject><subject>Protein Deglycase DJ-1</subject><subject>Protein Kinases - genetics</subject><subject>Ubiquitin-Protein Ligases - genetics</subject><issn>0885-3185</issn><issn>1531-8257</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUtv1DAUha0KRIfCgj9QZQOIRdprO35kWU2hIA1DJUqR2FhOcqMa8pjmeijz73E7A11VXV3p6Dv3cS5jrzgccQBx3Dd0JEAWco_NuJI8t0KZJ2wG1qpccqv22XOinwCcK66fsX2ulC1AwoydL8ff2GUrP_0KQ9avo49hHChrMGIdscmSukoaDpGymxCvMvRTt8kTgzE7v7PROLxNjkDoCV-wp63vCF_u6gH79uH9xfxjvvhy9ml-ssjrQgiZl8bLsuHKVF43BrAuvBat0ArKWkuuGs2NEUaWpqiqMu0LVaNAKy9UCbbl8oC92fZdTeP1Gim6PlCNXecHHNfktDHScm0fBQXnhS6tSuC7LVhPI9GErVtNoffTxnFwtzm7lLO7yzmxh7um66rH5p7cBZuA1zvAU-27dvJDHeie0xbSL263O95yN6HDzcMT3efTr_9G51tHoIh__jvSJ9LN0ij3fXnmfixPi8XFHNyl_Av8f6G9</recordid><startdate>200504</startdate><enddate>200504</enddate><creator>Bertoli-Avella, Aida M.</creator><creator>Giroud-Benitez, José L.</creator><creator>Akyol, Ali</creator><creator>Barbosa, Egberto</creator><creator>Schaap, Onno</creator><creator>van der Linde, Herma C.</creator><creator>Martignoni, Emilia</creator><creator>Lopiano, Leonardo</creator><creator>Lamberti, Paolo</creator><creator>Fincati, Emiliana</creator><creator>Antonini, Angelo</creator><creator>Stocchi, Fabrizio</creator><creator>Montagna, Pasquale</creator><creator>Squitieri, Ferdinando</creator><creator>Marini, Paolo</creator><creator>Abbruzzese, Giovanni</creator><creator>Fabbrini, Giovanni</creator><creator>Marconi, Roberto</creator><creator>Dalla Libera, Alessio</creator><creator>Trianni, Giorgio</creator><creator>Guidi, Marco</creator><creator>De Gaetano, Antonio</creator><creator>Boff Maegawa, Gustavo</creator><creator>De Leo, Antonino</creator><creator>Gallai, Virgilio</creator><creator>de Rosa, Giulia</creator><creator>Vanacore, Nicola</creator><creator>Meco, Giuseppe</creator><creator>van Duijn, Cornelia M.</creator><creator>Oostra, Ben A.</creator><creator>Heutink, Peter</creator><creator>Bonifati, Vincenzo</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Wiley</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>7X8</scope><scope>8BM</scope></search><sort><creationdate>200504</creationdate><title>Novel parkin mutations detected in patients with early-onset Parkinson's disease</title><author>Bertoli-Avella, Aida M. ; Giroud-Benitez, José L. ; Akyol, Ali ; Barbosa, Egberto ; Schaap, Onno ; van der Linde, Herma C. ; Martignoni, Emilia ; Lopiano, Leonardo ; Lamberti, Paolo ; Fincati, Emiliana ; Antonini, Angelo ; Stocchi, Fabrizio ; Montagna, Pasquale ; Squitieri, Ferdinando ; Marini, Paolo ; Abbruzzese, Giovanni ; Fabbrini, Giovanni ; Marconi, Roberto ; Dalla Libera, Alessio ; Trianni, Giorgio ; Guidi, Marco ; De Gaetano, Antonio ; Boff Maegawa, Gustavo ; De Leo, Antonino ; Gallai, Virgilio ; de Rosa, Giulia ; Vanacore, Nicola ; Meco, Giuseppe ; van Duijn, Cornelia M. ; Oostra, Ben A. ; Heutink, Peter ; Bonifati, Vincenzo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4223-97a39d157ba6d70ec4a62f26509c6315d6177273974bb91550bd5065a25908f13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Age of Onset</topic><topic>Aged</topic><topic>Biological and medical sciences</topic><topic>Cost-Benefit Analysis</topic><topic>Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases</topic><topic>early-onset</topic><topic>Exons - genetics</topic><topic>Female</topic><topic>gene dosage</topic><topic>Gene Library</topic><topic>Genotype</topic><topic>Humans</topic><topic>Intracellular Signaling Peptides and Proteins</topic><topic>Male</topic><topic>Mass Screening - methods</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis</topic><topic>mutation</topic><topic>Neurology</topic><topic>Oncogene Proteins - genetics</topic><topic>parkin</topic><topic>Parkinson Disease - economics</topic><topic>Parkinson Disease - epidemiology</topic><topic>Parkinson Disease - genetics</topic><topic>Parkinson's disease</topic><topic>Phenotype</topic><topic>Point Mutation - genetics</topic><topic>Polymerase Chain Reaction</topic><topic>Protein Deglycase DJ-1</topic><topic>Protein Kinases - genetics</topic><topic>Ubiquitin-Protein Ligases - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bertoli-Avella, Aida M.</creatorcontrib><creatorcontrib>Giroud-Benitez, José L.</creatorcontrib><creatorcontrib>Akyol, Ali</creatorcontrib><creatorcontrib>Barbosa, Egberto</creatorcontrib><creatorcontrib>Schaap, Onno</creatorcontrib><creatorcontrib>van der Linde, Herma C.</creatorcontrib><creatorcontrib>Martignoni, Emilia</creatorcontrib><creatorcontrib>Lopiano, Leonardo</creatorcontrib><creatorcontrib>Lamberti, Paolo</creatorcontrib><creatorcontrib>Fincati, Emiliana</creatorcontrib><creatorcontrib>Antonini, Angelo</creatorcontrib><creatorcontrib>Stocchi, Fabrizio</creatorcontrib><creatorcontrib>Montagna, Pasquale</creatorcontrib><creatorcontrib>Squitieri, Ferdinando</creatorcontrib><creatorcontrib>Marini, Paolo</creatorcontrib><creatorcontrib>Abbruzzese, Giovanni</creatorcontrib><creatorcontrib>Fabbrini, Giovanni</creatorcontrib><creatorcontrib>Marconi, Roberto</creatorcontrib><creatorcontrib>Dalla Libera, Alessio</creatorcontrib><creatorcontrib>Trianni, Giorgio</creatorcontrib><creatorcontrib>Guidi, Marco</creatorcontrib><creatorcontrib>De Gaetano, Antonio</creatorcontrib><creatorcontrib>Boff Maegawa, Gustavo</creatorcontrib><creatorcontrib>De Leo, Antonino</creatorcontrib><creatorcontrib>Gallai, Virgilio</creatorcontrib><creatorcontrib>de Rosa, Giulia</creatorcontrib><creatorcontrib>Vanacore, Nicola</creatorcontrib><creatorcontrib>Meco, Giuseppe</creatorcontrib><creatorcontrib>van Duijn, Cornelia M.</creatorcontrib><creatorcontrib>Oostra, Ben A.</creatorcontrib><creatorcontrib>Heutink, Peter</creatorcontrib><creatorcontrib>Bonifati, Vincenzo</creatorcontrib><creatorcontrib>Italian Parkinson Genetics Network, MD</creatorcontrib><creatorcontrib>The Italian Parkinson Genetics Network, MD</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><collection>ComDisDome</collection><jtitle>Movement disorders</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bertoli-Avella, Aida M.</au><au>Giroud-Benitez, José L.</au><au>Akyol, Ali</au><au>Barbosa, Egberto</au><au>Schaap, Onno</au><au>van der Linde, Herma C.</au><au>Martignoni, Emilia</au><au>Lopiano, Leonardo</au><au>Lamberti, Paolo</au><au>Fincati, Emiliana</au><au>Antonini, Angelo</au><au>Stocchi, Fabrizio</au><au>Montagna, Pasquale</au><au>Squitieri, Ferdinando</au><au>Marini, Paolo</au><au>Abbruzzese, Giovanni</au><au>Fabbrini, Giovanni</au><au>Marconi, Roberto</au><au>Dalla Libera, Alessio</au><au>Trianni, Giorgio</au><au>Guidi, Marco</au><au>De Gaetano, Antonio</au><au>Boff Maegawa, Gustavo</au><au>De Leo, Antonino</au><au>Gallai, Virgilio</au><au>de Rosa, Giulia</au><au>Vanacore, Nicola</au><au>Meco, Giuseppe</au><au>van Duijn, Cornelia M.</au><au>Oostra, Ben A.</au><au>Heutink, Peter</au><au>Bonifati, Vincenzo</au><aucorp>Italian Parkinson Genetics Network, MD</aucorp><aucorp>The Italian Parkinson Genetics Network, MD</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Novel parkin mutations detected in patients with early-onset Parkinson's disease</atitle><jtitle>Movement disorders</jtitle><addtitle>Mov. 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Fifteen parkin alterations (10 exon deletions and five point mutations) were identified, including four novel mutations: Arg402Cys, Cys418Arg, IVS11‐3C>G, and exon 8‐9‐10 deletion. Homozygous mutations, two heterozygous mutations, and a single heterozygous mutation were found in 8, 6, and 1 patient, respectively. Heterozygous exon deletions represented 28% of the mutant alleles. The patients with parkin mutations showed significantly earlier onset, longer disease duration, more frequently symmetric onset, and slower disease progression than the patients without mutations, in agreement with previous studies. This study confirms the frequent involvement of parkin and the importance of genetic testing in the diagnostic work‐up of EOP. © 2004 Movement Disorder Society</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>15584030</pmid><doi>10.1002/mds.20343</doi><tpages>8</tpages></addata></record> |
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| ispartof | Movement disorders, 2005-04, Vol.20 (4), p.424-431 |
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| subjects | Adolescent Adult Age of Onset Aged Biological and medical sciences Cost-Benefit Analysis Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases early-onset Exons - genetics Female gene dosage Gene Library Genotype Humans Intracellular Signaling Peptides and Proteins Male Mass Screening - methods Medical sciences Middle Aged Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis mutation Neurology Oncogene Proteins - genetics parkin Parkinson Disease - economics Parkinson Disease - epidemiology Parkinson Disease - genetics Parkinson's disease Phenotype Point Mutation - genetics Polymerase Chain Reaction Protein Deglycase DJ-1 Protein Kinases - genetics Ubiquitin-Protein Ligases - genetics |
| title | Novel parkin mutations detected in patients with early-onset Parkinson's disease |
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