Logo do repositório
 
Publicação

A blinded international study on the reliability of genetic testing for GGGGCC-repeat expansions in C9orf72 reveals marked differences in results among 14 laboratories

2014Artigo científico Acesso aberto
Ver registo simples
dc.contributor.authorAkimoto, Chizuru
dc.contributor.authorVolk, Alexander E.
dc.contributor.authorvan Blitterswijk, Marka
dc.contributor.authorVan den Broeck, Marleen
dc.contributor.authorLeblond, Claire S.
dc.contributor.authorLumbroso, Serge
dc.contributor.authorCamu, William
dc.contributor.authorNeitzel, Birgit
dc.contributor.authorOnodera, Osamu
dc.contributor.authorvan Rheenen, Wouter
dc.contributor.authorPinto, Susana
dc.contributor.authorWeber, Markus
dc.contributor.authorSmith, Bradley
dc.contributor.authorProven, Melanie
dc.contributor.authorTalbot, Kevin
dc.contributor.authorKeagle, Pamela
dc.contributor.authorChesi, Alessandra
dc.contributor.authorRatti, Antonia
dc.contributor.authorvan der Zee, Julie
dc.contributor.authorAlstermark, Helena
dc.contributor.authorBirve, Anna
dc.contributor.authorCalini, Daniela
dc.contributor.authorNordin, Angelica
dc.contributor.authorTradowsky, Daniela C.
dc.contributor.authorJust, Walter
dc.contributor.authorDaoud, Hussein
dc.contributor.authorAngerbauer, Sabrina
dc.contributor.authorDeJesus-Hernandez, Mariely
dc.contributor.authorKonno, Takuya
dc.contributor.authorLloyd-Jani, Anjali
dc.contributor.authorCarvalho, Mamede
dc.contributor.authorMouzat, Kevin
dc.contributor.authorLanders, John E.
dc.contributor.authorVeldink, Jan H.
dc.contributor.authorSilani, Vincenzo
dc.contributor.authorGitler, Aaron D.
dc.contributor.authorShaw, Christopher E.
dc.contributor.authorRouleau, Guy A
dc.contributor.authorvan den Berg, Leonard H.
dc.contributor.authorVan Broeckhoven, Christine
dc.contributor.authorRademakers, Rosa
dc.contributor.authorAndersen, Peter M.
dc.contributor.authorKubisch, Christian
dc.date.accessioned2022-02-08T15:38:37Z
dc.date.available2022-02-08T15:38:37Z
dc.date.issued2014
dc.descriptionCopyright © 2014, BMJ Publishing Group Ltd. All rights reserved. This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/pt_PT
dc.description.abstractBackground: The GGGGCC-repeat expansion in C9orf72 is the most frequent mutation found in patients with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Most of the studies on C9orf72 have relied on repeat-primed PCR (RP-PCR) methods for detection of the expansions. To investigate the inherent limitations of this technique, we compared methods and results of 14 laboratories. Methods: The 14 laboratories genotyped DNA from 78 individuals (diagnosed with ALS or FTD) in a blinded fashion. Eleven laboratories used a combination of amplicon-length analysis and RP-PCR, whereas three laboratories used RP-PCR alone; Southern blotting techniques were used as a reference. Results: Using PCR-based techniques, 5 of the 14 laboratories got results in full accordance with the Southern blotting results. Only 50 of the 78 DNA samples got the same genotype result in all 14 laboratories. There was a high degree of false positive and false negative results, and at least one sample could not be genotyped at all in 9 of the 14 laboratories. The mean sensitivity of a combination of amplicon-length analysis and RP-PCR was 95.0% (73.9-100%), and the mean specificity was 98.0% (87.5-100%). Overall, a sensitivity and specificity of more than 95% was observed in only seven laboratories. Conclusions: Because of the wide range seen in genotyping results, we recommend using a combination of amplicon-length analysis and RP-PCR as a minimum in a research setting. We propose that Southern blotting techniques should be the gold standard, and be made obligatory in a clinical diagnostic setting.pt_PT
dc.description.sponsorshipThis project was funded by the Swedish Science Council, the Brain Research Foundation, Mr B Hållsten's Brain Research Foundation, The Ulla-Carin Lindquist's Fundation for ALS Research, the Knut and Alice Wallenberg Foundation, Swedish Brain Power, the European Community's Health Seventh Framework Programme (FP7/2007–2013) (grant agreement no. 259867), The Belgian Science Policy Office Interuniversity Attraction Poles (IAP) programme, the Flemish Government supported Europe Initiative on Centers of Excellence in Neurodegeneration (CoEN), the Flemish Government initiated Methusalem excellence research programme, Alzheimer Research Foundation, the Medical Foundation Queen Elisabeth, the Research Foundation Flanders (FWO) and the FWO provided a postdoctoral scientist fellowship to JvdZ, University of Antwerp Research Fund, the Swiss ALS Foundation, the Italian Ministry of Health (RF-2009-1473856), Grant-in-Aid for the Research Committee of CNS Degenerative Diseases and Comprehensive Research on Disability Health and Welfare from the Ministry of Health, Labour and Welfare in Japan and Dr Van Blitterswijk is supported by the Milton Safenowitz Post-Doctoral Fellowship for ALS research from the ALS Association.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationJ Med Genet. 2014 Jun;51(6):419-424pt_PT
dc.identifier.doi10.1136/jmedgenet-2014-102360pt_PT
dc.identifier.eissn1468-6244
dc.identifier.issn0022-2593
dc.identifier.urihttp://hdl.handle.net/10451/51170
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherBMJ Publishing Grouppt_PT
dc.relationEuropean multidisciplinary ALS network identification to cure motor neuron degeneration
dc.relation.publisherversionhttps://jmg.bmj.com/pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/pt_PT
dc.subjectMolecular geneticspt_PT
dc.subjectMotor neurone diseasept_PT
dc.subjectNeurologypt_PT
dc.titleA blinded international study on the reliability of genetic testing for GGGGCC-repeat expansions in C9orf72 reveals marked differences in results among 14 laboratoriespt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardNumber259867
oaire.awardTitleEuropean multidisciplinary ALS network identification to cure motor neuron degeneration
oaire.awardURIinfo:eu-repo/grantAgreement/EC/FP7/259867/EU
oaire.citation.endPage424pt_PT
oaire.citation.issue6pt_PT
oaire.citation.startPage419pt_PT
oaire.citation.titleJournal of Medical Geneticspt_PT
oaire.citation.volume51pt_PT
oaire.fundingStreamFP7
person.familyNamePinto
person.familyNamede Carvalho
person.givenNameSusana
person.givenNameMamede
person.identifier593760
person.identifier.ciencia-idD31B-E89C-CB94
person.identifier.orcid0000-0002-0727-5897
person.identifier.orcid0000-0001-7556-0158
person.identifier.ridL-8394-2019
person.identifier.scopus-author-id23397978500
person.identifier.scopus-author-id7101893769
project.funder.identifierhttp://doi.org/10.13039/501100008530
project.funder.nameEuropean Commission
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication3fa09e71-c9b7-4536-a359-f7e3576dca09
relation.isAuthorOfPublicationdd7f55d4-c2b5-4fd2-9bd1-a9542a62f58f
relation.isAuthorOfPublication.latestForDiscovery3fa09e71-c9b7-4536-a359-f7e3576dca09
relation.isProjectOfPublication691b14ad-20c8-470f-849c-2fe0ae4e92a2
relation.isProjectOfPublication.latestForDiscovery691b14ad-20c8-470f-849c-2fe0ae4e92a2

Ficheiros

Principais
A mostrar 1 - 1 de 1
Miniatura
Nome:
C9orf72.pdf
Tamanho:
2.96 MB
Formato:
Adobe Portable Document Format
Ver/Abrir

Coleções

IMM - Artigos em Revistas Internacionais
FM - Artigos em Revistas Internacionais