Expanding the Clinical and Genetic Spectra of Primary Immunodeficiency-Related Disorders With Clinical Exome Sequencing
Primary immunodeficiencies (PIDs) refer to a clinically, immunologically, and genetically heterogeneous group of over 350 disorders affecting development or function of the immune system. The increasing use of next-generation sequencing (NGS) technology has greatly facilitated identification of gene...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2019 |
| País: | España |
| Institución: | Universitat Autònoma de Barcelona |
| Repositorio: | Dipòsit Digital de Documents de la UAB |
| Idioma: | inglés |
| OAI Identifier: | oai:ddd.uab.cat:223391 |
| Acceso en línea: | https://ddd.uab.cat/record/223391 https://dx.doi.org/urn:doi:10.3389/fimmu.2019.02325 |
| Access Level: | acceso abierto |
| Palabra clave: | Primary immunodeficiencies Next generation sequencing Clinical exome sequencing TruSight one Sequencing panel Mutations Genetic variants |
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Expanding the Clinical and Genetic Spectra of Primary Immunodeficiency-Related Disorders With Clinical Exome SequencingExpected and Unexpected FindingsRudilla, FrancescFranco-Jarava, Clara|||0000-0002-9788-189XMartínez Gallo, Mónica|||0000-0002-7340-2161Garcia-Prat, Marina|||0000-0001-5387-1908Martín-Nalda, Andrea|||0000-0002-1715-153XRivière, JacquesAguiló-Cucurull, Aina|||0000-0001-5622-778XMongay, LauraVidal, Francisco|||0000-0001-8089-4945Solanich, Xavier|||0000-0002-2572-2187Irastorza, IñakiSantos-Pérez, Juan LuisTercedor Sánchez, JesúsCusco, Ivon|||0000-0003-2104-9332Serra, ClaraBaz-Redón, Noelia|||0000-0003-1704-3413Fernández Cancio, Mónica|||0000-0003-1872-3488Carreras, CarmenVagace, ManuelGarcía-Patos Briones, Vicente|||0000-0003-1654-6035Pujol-Borrell, Ricardo|||0000-0001-7833-675XSoler-Palacín, Pere|||0000-0002-0346-5570Colobrán Oriol, Roger|||0000-0002-5964-536XPrimary immunodeficienciesNext generation sequencingClinical exome sequencingTruSight oneSequencing panelMutationsGenetic variantsPrimary immunodeficiencies (PIDs) refer to a clinically, immunologically, and genetically heterogeneous group of over 350 disorders affecting development or function of the immune system. The increasing use of next-generation sequencing (NGS) technology has greatly facilitated identification of genetic defects in PID patients in daily clinical practice. Several NGS approaches are available, from the unbiased whole exome sequencing (WES) to specific gene panels. Here, we report on a 3-year experience with clinical exome sequencing (CES) for genetic diagnosis of PIDs. We used the TruSight One sequencing panel, which includes 4,813 disease-associated genes, in 61 unrelated patients (pediatric and adults). The analysis was done in 2 steps: first, we focused on a virtual PID panel and then, we expanded the analysis to the remaining genes. A molecular diagnosis was achieved in 19 (31%) patients: 12 (20%) with mutations in genes included in the virtual PID panel and 7 (11%) with mutations in other genes. These latter cases provided interesting and somewhat unexpected findings that expand the clinical and genetic spectra of PID-related disorders, and are useful to consider in the differential diagnosis. We also discuss 5 patients (8%) with incomplete genotypes or variants of uncertain significance. Finally, we address the limitations of CES exemplified by 7 patients (11%) with negative results on CES who were later diagnosed by other approaches (more specific PID panels, WES, and comparative genomic hybridization array). In summary, the genetic diagnosis rate using CES was 31% (including a description of 12 novel mutations), which rose to 42% after including diagnoses achieved by later use of other techniques. The description of patients with mutations in genes not included in the PID classification illustrates the heterogeneity and complexity of PID-related disorders.Universitat Autònoma de Barcelona 22019-01-0120192019-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/223391https://dx.doi.org/urn:doi:10.3389/fimmu.2019.02325reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengInstituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI14-00405Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI17-00660open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2233912026-06-06T12:50:31Z |
| dc.title.none.fl_str_mv |
Expanding the Clinical and Genetic Spectra of Primary Immunodeficiency-Related Disorders With Clinical Exome Sequencing Expected and Unexpected Findings |
| title |
Expanding the Clinical and Genetic Spectra of Primary Immunodeficiency-Related Disorders With Clinical Exome Sequencing |
| spellingShingle |
Expanding the Clinical and Genetic Spectra of Primary Immunodeficiency-Related Disorders With Clinical Exome Sequencing Rudilla, Francesc Primary immunodeficiencies Next generation sequencing Clinical exome sequencing TruSight one Sequencing panel Mutations Genetic variants |
| title_short |
Expanding the Clinical and Genetic Spectra of Primary Immunodeficiency-Related Disorders With Clinical Exome Sequencing |
| title_full |
Expanding the Clinical and Genetic Spectra of Primary Immunodeficiency-Related Disorders With Clinical Exome Sequencing |
| title_fullStr |
Expanding the Clinical and Genetic Spectra of Primary Immunodeficiency-Related Disorders With Clinical Exome Sequencing |
| title_full_unstemmed |
Expanding the Clinical and Genetic Spectra of Primary Immunodeficiency-Related Disorders With Clinical Exome Sequencing |
| title_sort |
Expanding the Clinical and Genetic Spectra of Primary Immunodeficiency-Related Disorders With Clinical Exome Sequencing |
| dc.creator.none.fl_str_mv |
Rudilla, Francesc Franco-Jarava, Clara|||0000-0002-9788-189X Martínez Gallo, Mónica|||0000-0002-7340-2161 Garcia-Prat, Marina|||0000-0001-5387-1908 Martín-Nalda, Andrea|||0000-0002-1715-153X Rivière, Jacques Aguiló-Cucurull, Aina|||0000-0001-5622-778X Mongay, Laura Vidal, Francisco|||0000-0001-8089-4945 Solanich, Xavier|||0000-0002-2572-2187 Irastorza, Iñaki Santos-Pérez, Juan Luis Tercedor Sánchez, Jesús Cusco, Ivon|||0000-0003-2104-9332 Serra, Clara Baz-Redón, Noelia|||0000-0003-1704-3413 Fernández Cancio, Mónica|||0000-0003-1872-3488 Carreras, Carmen Vagace, Manuel García-Patos Briones, Vicente|||0000-0003-1654-6035 Pujol-Borrell, Ricardo|||0000-0001-7833-675X Soler-Palacín, Pere|||0000-0002-0346-5570 Colobrán Oriol, Roger|||0000-0002-5964-536X |
| author |
Rudilla, Francesc |
| author_facet |
Rudilla, Francesc Franco-Jarava, Clara|||0000-0002-9788-189X Martínez Gallo, Mónica|||0000-0002-7340-2161 Garcia-Prat, Marina|||0000-0001-5387-1908 Martín-Nalda, Andrea|||0000-0002-1715-153X Rivière, Jacques Aguiló-Cucurull, Aina|||0000-0001-5622-778X Mongay, Laura Vidal, Francisco|||0000-0001-8089-4945 Solanich, Xavier|||0000-0002-2572-2187 Irastorza, Iñaki Santos-Pérez, Juan Luis Tercedor Sánchez, Jesús Cusco, Ivon|||0000-0003-2104-9332 Serra, Clara Baz-Redón, Noelia|||0000-0003-1704-3413 Fernández Cancio, Mónica|||0000-0003-1872-3488 Carreras, Carmen Vagace, Manuel García-Patos Briones, Vicente|||0000-0003-1654-6035 Pujol-Borrell, Ricardo|||0000-0001-7833-675X Soler-Palacín, Pere|||0000-0002-0346-5570 Colobrán Oriol, Roger|||0000-0002-5964-536X |
| author_role |
author |
| author2 |
Franco-Jarava, Clara|||0000-0002-9788-189X Martínez Gallo, Mónica|||0000-0002-7340-2161 Garcia-Prat, Marina|||0000-0001-5387-1908 Martín-Nalda, Andrea|||0000-0002-1715-153X Rivière, Jacques Aguiló-Cucurull, Aina|||0000-0001-5622-778X Mongay, Laura Vidal, Francisco|||0000-0001-8089-4945 Solanich, Xavier|||0000-0002-2572-2187 Irastorza, Iñaki Santos-Pérez, Juan Luis Tercedor Sánchez, Jesús Cusco, Ivon|||0000-0003-2104-9332 Serra, Clara Baz-Redón, Noelia|||0000-0003-1704-3413 Fernández Cancio, Mónica|||0000-0003-1872-3488 Carreras, Carmen Vagace, Manuel García-Patos Briones, Vicente|||0000-0003-1654-6035 Pujol-Borrell, Ricardo|||0000-0001-7833-675X Soler-Palacín, Pere|||0000-0002-0346-5570 Colobrán Oriol, Roger|||0000-0002-5964-536X |
| author2_role |
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 |
Universitat Autònoma de Barcelona |
| dc.subject.none.fl_str_mv |
Primary immunodeficiencies Next generation sequencing Clinical exome sequencing TruSight one Sequencing panel Mutations Genetic variants |
| topic |
Primary immunodeficiencies Next generation sequencing Clinical exome sequencing TruSight one Sequencing panel Mutations Genetic variants |
| description |
Primary immunodeficiencies (PIDs) refer to a clinically, immunologically, and genetically heterogeneous group of over 350 disorders affecting development or function of the immune system. The increasing use of next-generation sequencing (NGS) technology has greatly facilitated identification of genetic defects in PID patients in daily clinical practice. Several NGS approaches are available, from the unbiased whole exome sequencing (WES) to specific gene panels. Here, we report on a 3-year experience with clinical exome sequencing (CES) for genetic diagnosis of PIDs. We used the TruSight One sequencing panel, which includes 4,813 disease-associated genes, in 61 unrelated patients (pediatric and adults). The analysis was done in 2 steps: first, we focused on a virtual PID panel and then, we expanded the analysis to the remaining genes. A molecular diagnosis was achieved in 19 (31%) patients: 12 (20%) with mutations in genes included in the virtual PID panel and 7 (11%) with mutations in other genes. These latter cases provided interesting and somewhat unexpected findings that expand the clinical and genetic spectra of PID-related disorders, and are useful to consider in the differential diagnosis. We also discuss 5 patients (8%) with incomplete genotypes or variants of uncertain significance. Finally, we address the limitations of CES exemplified by 7 patients (11%) with negative results on CES who were later diagnosed by other approaches (more specific PID panels, WES, and comparative genomic hybridization array). In summary, the genetic diagnosis rate using CES was 31% (including a description of 12 novel mutations), which rose to 42% after including diagnoses achieved by later use of other techniques. The description of patients with mutations in genes not included in the PID classification illustrates the heterogeneity and complexity of PID-related disorders. |
| publishDate |
2019 |
| dc.date.none.fl_str_mv |
2 2019-01-01 2019 2019-01-01 |
| dc.type.none.fl_str_mv |
Article http://purl.org/coar/resource_type/c_6501 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
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article |
| dc.identifier.none.fl_str_mv |
https://ddd.uab.cat/record/223391 https://dx.doi.org/urn:doi:10.3389/fimmu.2019.02325 |
| url |
https://ddd.uab.cat/record/223391 https://dx.doi.org/urn:doi:10.3389/fimmu.2019.02325 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.relation.none.fl_str_mv |
Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI14-00405 Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI17-00660 |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/ |
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info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/ |
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openAccess |
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application/pdf |
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reponame:Dipòsit Digital de Documents de la UAB instname:Universitat Autònoma de Barcelona |
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Universitat Autònoma de Barcelona |
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Dipòsit Digital de Documents de la UAB |
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