A blinded international study on the reliability of genetic testing for GGGGCC-repeat expansions in C9orf72 reveals marked differences in results among 14 laboratories
| Autor(a) principal: | |
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| Data de Publicação: | 2014 |
| Outros Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Texto Completo: | http://hdl.handle.net/10451/51170 |
Resumo: | Copyright © 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/ |
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A blinded international study on the reliability of genetic testing for GGGGCC-repeat expansions in C9orf72 reveals marked differences in results among 14 laboratoriesMolecular geneticsMotor neurone diseaseNeurologyCopyright © 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/Background: 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.This 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.BMJ Publishing GroupRepositório da Universidade de LisboaAkimoto, ChizuruVolk, Alexander E.van Blitterswijk, MarkaVan den Broeck, MarleenLeblond, Claire S.Lumbroso, SergeCamu, WilliamNeitzel, BirgitOnodera, Osamuvan Rheenen, WouterPinto, SusanaWeber, MarkusSmith, BradleyProven, MelanieTalbot, KevinKeagle, PamelaChesi, AlessandraRatti, Antoniavan der Zee, JulieAlstermark, HelenaBirve, AnnaCalini, DanielaNordin, AngelicaTradowsky, Daniela C.Just, WalterDaoud, HusseinAngerbauer, SabrinaDeJesus-Hernandez, MarielyKonno, TakuyaLloyd-Jani, AnjaliCarvalho, MamedeMouzat, KevinLanders, John E.Veldink, Jan H.Silani, VincenzoGitler, Aaron D.Shaw, Christopher E.Rouleau, Guy Avan den Berg, Leonard H.Van Broeckhoven, ChristineRademakers, RosaAndersen, Peter M.Kubisch, Christian2022-02-08T15:38:37Z20142014-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/51170engJ Med Genet. 2014 Jun;51(6):419-4240022-259310.1136/jmedgenet-2014-1023601468-6244info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T16:55:42Zoai:repositorio.ul.pt:10451/51170Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:02:28.837063Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
| dc.title.none.fl_str_mv |
A blinded international study on the reliability of genetic testing for GGGGCC-repeat expansions in C9orf72 reveals marked differences in results among 14 laboratories |
| title |
A blinded international study on the reliability of genetic testing for GGGGCC-repeat expansions in C9orf72 reveals marked differences in results among 14 laboratories |
| spellingShingle |
A blinded international study on the reliability of genetic testing for GGGGCC-repeat expansions in C9orf72 reveals marked differences in results among 14 laboratories Akimoto, Chizuru Molecular genetics Motor neurone disease Neurology |
| title_short |
A blinded international study on the reliability of genetic testing for GGGGCC-repeat expansions in C9orf72 reveals marked differences in results among 14 laboratories |
| title_full |
A blinded international study on the reliability of genetic testing for GGGGCC-repeat expansions in C9orf72 reveals marked differences in results among 14 laboratories |
| title_fullStr |
A blinded international study on the reliability of genetic testing for GGGGCC-repeat expansions in C9orf72 reveals marked differences in results among 14 laboratories |
| title_full_unstemmed |
A blinded international study on the reliability of genetic testing for GGGGCC-repeat expansions in C9orf72 reveals marked differences in results among 14 laboratories |
| title_sort |
A blinded international study on the reliability of genetic testing for GGGGCC-repeat expansions in C9orf72 reveals marked differences in results among 14 laboratories |
| author |
Akimoto, Chizuru |
| author_facet |
Akimoto, Chizuru Volk, Alexander E. van Blitterswijk, Marka Van den Broeck, Marleen Leblond, Claire S. Lumbroso, Serge Camu, William Neitzel, Birgit Onodera, Osamu van Rheenen, Wouter Pinto, Susana Weber, Markus Smith, Bradley Proven, Melanie Talbot, Kevin Keagle, Pamela Chesi, Alessandra Ratti, Antonia van der Zee, Julie Alstermark, Helena Birve, Anna Calini, Daniela Nordin, Angelica Tradowsky, Daniela C. Just, Walter Daoud, Hussein Angerbauer, Sabrina DeJesus-Hernandez, Mariely Konno, Takuya Lloyd-Jani, Anjali Carvalho, Mamede Mouzat, Kevin Landers, John E. Veldink, Jan H. Silani, Vincenzo Gitler, Aaron D. Shaw, Christopher E. Rouleau, Guy A van den Berg, Leonard H. Van Broeckhoven, Christine Rademakers, Rosa Andersen, Peter M. Kubisch, Christian |
| author_role |
author |
| author2 |
Volk, Alexander E. van Blitterswijk, Marka Van den Broeck, Marleen Leblond, Claire S. Lumbroso, Serge Camu, William Neitzel, Birgit Onodera, Osamu van Rheenen, Wouter Pinto, Susana Weber, Markus Smith, Bradley Proven, Melanie Talbot, Kevin Keagle, Pamela Chesi, Alessandra Ratti, Antonia van der Zee, Julie Alstermark, Helena Birve, Anna Calini, Daniela Nordin, Angelica Tradowsky, Daniela C. Just, Walter Daoud, Hussein Angerbauer, Sabrina DeJesus-Hernandez, Mariely Konno, Takuya Lloyd-Jani, Anjali Carvalho, Mamede Mouzat, Kevin Landers, John E. Veldink, Jan H. Silani, Vincenzo Gitler, Aaron D. Shaw, Christopher E. Rouleau, Guy A van den Berg, Leonard H. Van Broeckhoven, Christine Rademakers, Rosa Andersen, Peter M. Kubisch, Christian |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Repositório da Universidade de Lisboa |
| dc.contributor.author.fl_str_mv |
Akimoto, Chizuru Volk, Alexander E. van Blitterswijk, Marka Van den Broeck, Marleen Leblond, Claire S. Lumbroso, Serge Camu, William Neitzel, Birgit Onodera, Osamu van Rheenen, Wouter Pinto, Susana Weber, Markus Smith, Bradley Proven, Melanie Talbot, Kevin Keagle, Pamela Chesi, Alessandra Ratti, Antonia van der Zee, Julie Alstermark, Helena Birve, Anna Calini, Daniela Nordin, Angelica Tradowsky, Daniela C. Just, Walter Daoud, Hussein Angerbauer, Sabrina DeJesus-Hernandez, Mariely Konno, Takuya Lloyd-Jani, Anjali Carvalho, Mamede Mouzat, Kevin Landers, John E. Veldink, Jan H. Silani, Vincenzo Gitler, Aaron D. Shaw, Christopher E. Rouleau, Guy A van den Berg, Leonard H. Van Broeckhoven, Christine Rademakers, Rosa Andersen, Peter M. Kubisch, Christian |
| dc.subject.por.fl_str_mv |
Molecular genetics Motor neurone disease Neurology |
| topic |
Molecular genetics Motor neurone disease Neurology |
| description |
Copyright © 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/ |
| publishDate |
2014 |
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2014 2014-01-01T00:00:00Z 2022-02-08T15:38:37Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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http://hdl.handle.net/10451/51170 |
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http://hdl.handle.net/10451/51170 |
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eng |
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eng |
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J Med Genet. 2014 Jun;51(6):419-424 0022-2593 10.1136/jmedgenet-2014-102360 1468-6244 |
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BMJ Publishing Group |
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BMJ Publishing Group |
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