Targeted Gene Panel Sequencing for Early-onset Inflammatory Bowel Disease and Chronic Diarrhea
Autor(a) principal: | |
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Data de Publicação: | 2017 |
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/10400.17/4726 |
Resumo: | Background: In contrast to adult-onset inflammatory bowel disease (IBD), where many genetic loci have been shown to be involved in complex disease etiology, early-onset IBD (eoIBD) and associated syndromes can sometimes present as monogenic conditions. As a result, the clinical phenotype and ideal disease management in these patients often differ from those in adult-onset IBD. However, due to high costs and the complexity of data analysis, high-throughput screening for genetic causes has not yet become a standard part of the diagnostic work-up of eoIBD patients. Methods: We selected 28 genes of interest associated with monogenic IBD and performed targeted panel sequencing in 71 patients diagnosed with eoIBD or early-onset chronic diarrhea to detect causative variants. We compared these results to whole-exome sequencing (WES) data available for 25 of these patients. Results: Target coverage was significantly higher in the targeted gene panel approach compared with WES, whereas the cost of the panel was considerably lower (approximately 25% of WES). Disease-causing variants affecting protein function were identified in 5 patients (7%), located in genes of the IL10 signaling pathway (3), WAS (1), and DKC1 (1). The functional effects of 8 candidate variants in 5 additional patients (7%) are under further investigation. WES did not identify additional causative mutations in 25 patients. Conclusions: Targeted gene panel sequencing is a fast and effective screening method for monogenic causes of eoIBD that should be routinely established in national referral centers. |
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Targeted Gene Panel Sequencing for Early-onset Inflammatory Bowel Disease and Chronic DiarrheaChild, PreschoolChildChronic DiseaseDiarrhea / etiology*Exome SequencingGenetic Predisposition to Disease*Genome-Wide Association StudyHigh-Throughput Nucleotide SequencingInfant, NewbornInflammatory Bowel Diseases / genetics*MutationHDE PEDBackground: In contrast to adult-onset inflammatory bowel disease (IBD), where many genetic loci have been shown to be involved in complex disease etiology, early-onset IBD (eoIBD) and associated syndromes can sometimes present as monogenic conditions. As a result, the clinical phenotype and ideal disease management in these patients often differ from those in adult-onset IBD. However, due to high costs and the complexity of data analysis, high-throughput screening for genetic causes has not yet become a standard part of the diagnostic work-up of eoIBD patients. Methods: We selected 28 genes of interest associated with monogenic IBD and performed targeted panel sequencing in 71 patients diagnosed with eoIBD or early-onset chronic diarrhea to detect causative variants. We compared these results to whole-exome sequencing (WES) data available for 25 of these patients. Results: Target coverage was significantly higher in the targeted gene panel approach compared with WES, whereas the cost of the panel was considerably lower (approximately 25% of WES). Disease-causing variants affecting protein function were identified in 5 patients (7%), located in genes of the IL10 signaling pathway (3), WAS (1), and DKC1 (1). The functional effects of 8 candidate variants in 5 additional patients (7%) are under further investigation. WES did not identify additional causative mutations in 25 patients. Conclusions: Targeted gene panel sequencing is a fast and effective screening method for monogenic causes of eoIBD that should be routinely established in national referral centers.Oxford University PressRepositório do Centro Hospitalar Universitário de Lisboa Central, EPEPetersen, BSAugust, DAbt, RAlddafari, MAtarod, LBaris, SBhavsar, HBrinkert, FBuchta, MBulashevska, AChee, RCordeiro, AIDara, NDückers, GElmarsafy, AFrede, NGalal, NGerner, PGlocker, EOGoldacker, SHammermann, JHasselblatt, PHavlicekova, ZHübscher, KJesenak, MKaraca, NEKarakoc-Aydiner, EKharaghani, MMKilic, SSKiykim, AKlein, CKlemann, CKobbe, RKotlarz, DLaass, MWLeahy, TRMesdaghi, MMitton, SFarela Neves, JÖztürk, BPereira, LFRohr, JRestrepo, JLRRuzaike, GSaleh, NSeneviratne, SSenol, ESpeckmann, CTegtmeyer, DThankam, Pvan der Werff ten Bosch, Jvon Bernuth, HZeissig, SZeissig, YFranke, AGrimbacher, B2023-11-03T10:50:09Z20172017-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.17/4726engInflamm Bowel Dis . 2017 Dec;23(12):2109-212010.1097/MIB.0000000000001235info: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:RCAAP2023-11-05T06:33:11Zoai:repositorio.chlc.min-saude.pt:10400.17/4726Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:26:49.829490Repositório 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 |
Targeted Gene Panel Sequencing for Early-onset Inflammatory Bowel Disease and Chronic Diarrhea |
title |
Targeted Gene Panel Sequencing for Early-onset Inflammatory Bowel Disease and Chronic Diarrhea |
spellingShingle |
Targeted Gene Panel Sequencing for Early-onset Inflammatory Bowel Disease and Chronic Diarrhea Petersen, BS Child, Preschool Child Chronic Disease Diarrhea / etiology* Exome Sequencing Genetic Predisposition to Disease* Genome-Wide Association Study High-Throughput Nucleotide Sequencing Infant, Newborn Inflammatory Bowel Diseases / genetics* Mutation HDE PED |
title_short |
Targeted Gene Panel Sequencing for Early-onset Inflammatory Bowel Disease and Chronic Diarrhea |
title_full |
Targeted Gene Panel Sequencing for Early-onset Inflammatory Bowel Disease and Chronic Diarrhea |
title_fullStr |
Targeted Gene Panel Sequencing for Early-onset Inflammatory Bowel Disease and Chronic Diarrhea |
title_full_unstemmed |
Targeted Gene Panel Sequencing for Early-onset Inflammatory Bowel Disease and Chronic Diarrhea |
title_sort |
Targeted Gene Panel Sequencing for Early-onset Inflammatory Bowel Disease and Chronic Diarrhea |
author |
Petersen, BS |
author_facet |
Petersen, BS August, D Abt, R Alddafari, M Atarod, L Baris, S Bhavsar, H Brinkert, F Buchta, M Bulashevska, A Chee, R Cordeiro, AI Dara, N Dückers, G Elmarsafy, A Frede, N Galal, N Gerner, P Glocker, EO Goldacker, S Hammermann, J Hasselblatt, P Havlicekova, Z Hübscher, K Jesenak, M Karaca, NE Karakoc-Aydiner, E Kharaghani, MM Kilic, SS Kiykim, A Klein, C Klemann, C Kobbe, R Kotlarz, D Laass, MW Leahy, TR Mesdaghi, M Mitton, S Farela Neves, J Öztürk, B Pereira, LF Rohr, J Restrepo, JLR Ruzaike, G Saleh, N Seneviratne, S Senol, E Speckmann, C Tegtmeyer, D Thankam, P van der Werff ten Bosch, J von Bernuth, H Zeissig, S Zeissig, Y Franke, A Grimbacher, B |
author_role |
author |
author2 |
August, D Abt, R Alddafari, M Atarod, L Baris, S Bhavsar, H Brinkert, F Buchta, M Bulashevska, A Chee, R Cordeiro, AI Dara, N Dückers, G Elmarsafy, A Frede, N Galal, N Gerner, P Glocker, EO Goldacker, S Hammermann, J Hasselblatt, P Havlicekova, Z Hübscher, K Jesenak, M Karaca, NE Karakoc-Aydiner, E Kharaghani, MM Kilic, SS Kiykim, A Klein, C Klemann, C Kobbe, R Kotlarz, D Laass, MW Leahy, TR Mesdaghi, M Mitton, S Farela Neves, J Öztürk, B Pereira, LF Rohr, J Restrepo, JLR Ruzaike, G Saleh, N Seneviratne, S Senol, E Speckmann, C Tegtmeyer, D Thankam, P van der Werff ten Bosch, J von Bernuth, H Zeissig, S Zeissig, Y Franke, A Grimbacher, B |
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 author author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Repositório do Centro Hospitalar Universitário de Lisboa Central, EPE |
dc.contributor.author.fl_str_mv |
Petersen, BS August, D Abt, R Alddafari, M Atarod, L Baris, S Bhavsar, H Brinkert, F Buchta, M Bulashevska, A Chee, R Cordeiro, AI Dara, N Dückers, G Elmarsafy, A Frede, N Galal, N Gerner, P Glocker, EO Goldacker, S Hammermann, J Hasselblatt, P Havlicekova, Z Hübscher, K Jesenak, M Karaca, NE Karakoc-Aydiner, E Kharaghani, MM Kilic, SS Kiykim, A Klein, C Klemann, C Kobbe, R Kotlarz, D Laass, MW Leahy, TR Mesdaghi, M Mitton, S Farela Neves, J Öztürk, B Pereira, LF Rohr, J Restrepo, JLR Ruzaike, G Saleh, N Seneviratne, S Senol, E Speckmann, C Tegtmeyer, D Thankam, P van der Werff ten Bosch, J von Bernuth, H Zeissig, S Zeissig, Y Franke, A Grimbacher, B |
dc.subject.por.fl_str_mv |
Child, Preschool Child Chronic Disease Diarrhea / etiology* Exome Sequencing Genetic Predisposition to Disease* Genome-Wide Association Study High-Throughput Nucleotide Sequencing Infant, Newborn Inflammatory Bowel Diseases / genetics* Mutation HDE PED |
topic |
Child, Preschool Child Chronic Disease Diarrhea / etiology* Exome Sequencing Genetic Predisposition to Disease* Genome-Wide Association Study High-Throughput Nucleotide Sequencing Infant, Newborn Inflammatory Bowel Diseases / genetics* Mutation HDE PED |
description |
Background: In contrast to adult-onset inflammatory bowel disease (IBD), where many genetic loci have been shown to be involved in complex disease etiology, early-onset IBD (eoIBD) and associated syndromes can sometimes present as monogenic conditions. As a result, the clinical phenotype and ideal disease management in these patients often differ from those in adult-onset IBD. However, due to high costs and the complexity of data analysis, high-throughput screening for genetic causes has not yet become a standard part of the diagnostic work-up of eoIBD patients. Methods: We selected 28 genes of interest associated with monogenic IBD and performed targeted panel sequencing in 71 patients diagnosed with eoIBD or early-onset chronic diarrhea to detect causative variants. We compared these results to whole-exome sequencing (WES) data available for 25 of these patients. Results: Target coverage was significantly higher in the targeted gene panel approach compared with WES, whereas the cost of the panel was considerably lower (approximately 25% of WES). Disease-causing variants affecting protein function were identified in 5 patients (7%), located in genes of the IL10 signaling pathway (3), WAS (1), and DKC1 (1). The functional effects of 8 candidate variants in 5 additional patients (7%) are under further investigation. WES did not identify additional causative mutations in 25 patients. Conclusions: Targeted gene panel sequencing is a fast and effective screening method for monogenic causes of eoIBD that should be routinely established in national referral centers. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017 2017-01-01T00:00:00Z 2023-11-03T10:50:09Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.17/4726 |
url |
http://hdl.handle.net/10400.17/4726 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Inflamm Bowel Dis . 2017 Dec;23(12):2109-2120 10.1097/MIB.0000000000001235 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Oxford University Press |
publisher.none.fl_str_mv |
Oxford University Press |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799134150204063744 |