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Next Generation Sequencing for Detecting Somatic FAS Mutations in Patients With Autoimmune Lymphoproliferative Syndrome

Autoimmune lymphoproliferative syndrome (ALPS) is a primary immune regulatory disorder clinically defined by chronic and benign lymphoproliferation, autoimmunity and an increased risk of lymphoma due to a genetic defect in the FAS-FASL apoptotic pathway. Genetic defects associated with ALPS are germ...

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Autores principales: López-Nevado, Marta, Docampo-Cordeiro, Jorge, Ramos, José T., Rodríguez-Pena, Rebeca, Gil-López, Celia, Sánchez-Ramón, Silvia, Gil-Herrera, Juana, Díaz-Madroñero, María J., Delgado-Martín, María A., Morales-Pérez, Pablo, Paz-Artal, Estela, Magerus, Aude, Rieux-Laucat, Frederic, Allende, Luis M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117005/
https://www.ncbi.nlm.nih.gov/pubmed/33995372
http://dx.doi.org/10.3389/fimmu.2021.656356
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author López-Nevado, Marta
Docampo-Cordeiro, Jorge
Ramos, José T.
Rodríguez-Pena, Rebeca
Gil-López, Celia
Sánchez-Ramón, Silvia
Gil-Herrera, Juana
Díaz-Madroñero, María J.
Delgado-Martín, María A.
Morales-Pérez, Pablo
Paz-Artal, Estela
Magerus, Aude
Rieux-Laucat, Frederic
Allende, Luis M.
author_facet López-Nevado, Marta
Docampo-Cordeiro, Jorge
Ramos, José T.
Rodríguez-Pena, Rebeca
Gil-López, Celia
Sánchez-Ramón, Silvia
Gil-Herrera, Juana
Díaz-Madroñero, María J.
Delgado-Martín, María A.
Morales-Pérez, Pablo
Paz-Artal, Estela
Magerus, Aude
Rieux-Laucat, Frederic
Allende, Luis M.
author_sort López-Nevado, Marta
collection PubMed
description Autoimmune lymphoproliferative syndrome (ALPS) is a primary immune regulatory disorder clinically defined by chronic and benign lymphoproliferation, autoimmunity and an increased risk of lymphoma due to a genetic defect in the FAS-FASL apoptotic pathway. Genetic defects associated with ALPS are germinal and somatic mutations in FAS gene, in addition to germinal mutations in FASLG, FADD, CASP8 and CASP10 genes. The accumulation of CD3+TCRαβ+CD4-CD8- double negative T-cells (DNT) is a hallmark of the disease and 20-25% of ALPS patients show heterozygous somatic mutations restricted to DNT in the FAS gene (ALPS-sFAS patients). Nowadays, somatic mutations in the FAS gene are detected through Sanger sequencing in isolated DNT. In this study, we report an ALPS-sFAS patient fulfilling clinical and laboratory ALPS criteria, who was diagnosed through NGS with a targeted gene panel using DNA from whole blood. Data analysis was carried out with Torrent Suite Software and variant detection was performed by both germinal and somatic variant caller plugin. The somatic variant caller correctly detected other six ALPS-sFAS patients previously diagnosed in the authors’ laboratories. In summary, this approach allows the detection of both germline and somatic mutations related to ALPS by NGS, avoiding the isolation of DNT as the first step. The reads of the somatic variants could be detected even in patients with DNT in the cut off limit. Thus, custom-designed NGS panel testing may be a faster and more reliable method for the diagnosis of new ALPS patients, including those with somatic FAS mutations (ALPS-sFAS).
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spelling pubmed-81170052021-05-14 Next Generation Sequencing for Detecting Somatic FAS Mutations in Patients With Autoimmune Lymphoproliferative Syndrome López-Nevado, Marta Docampo-Cordeiro, Jorge Ramos, José T. Rodríguez-Pena, Rebeca Gil-López, Celia Sánchez-Ramón, Silvia Gil-Herrera, Juana Díaz-Madroñero, María J. Delgado-Martín, María A. Morales-Pérez, Pablo Paz-Artal, Estela Magerus, Aude Rieux-Laucat, Frederic Allende, Luis M. Front Immunol Immunology Autoimmune lymphoproliferative syndrome (ALPS) is a primary immune regulatory disorder clinically defined by chronic and benign lymphoproliferation, autoimmunity and an increased risk of lymphoma due to a genetic defect in the FAS-FASL apoptotic pathway. Genetic defects associated with ALPS are germinal and somatic mutations in FAS gene, in addition to germinal mutations in FASLG, FADD, CASP8 and CASP10 genes. The accumulation of CD3+TCRαβ+CD4-CD8- double negative T-cells (DNT) is a hallmark of the disease and 20-25% of ALPS patients show heterozygous somatic mutations restricted to DNT in the FAS gene (ALPS-sFAS patients). Nowadays, somatic mutations in the FAS gene are detected through Sanger sequencing in isolated DNT. In this study, we report an ALPS-sFAS patient fulfilling clinical and laboratory ALPS criteria, who was diagnosed through NGS with a targeted gene panel using DNA from whole blood. Data analysis was carried out with Torrent Suite Software and variant detection was performed by both germinal and somatic variant caller plugin. The somatic variant caller correctly detected other six ALPS-sFAS patients previously diagnosed in the authors’ laboratories. In summary, this approach allows the detection of both germline and somatic mutations related to ALPS by NGS, avoiding the isolation of DNT as the first step. The reads of the somatic variants could be detected even in patients with DNT in the cut off limit. Thus, custom-designed NGS panel testing may be a faster and more reliable method for the diagnosis of new ALPS patients, including those with somatic FAS mutations (ALPS-sFAS). Frontiers Media S.A. 2021-04-29 /pmc/articles/PMC8117005/ /pubmed/33995372 http://dx.doi.org/10.3389/fimmu.2021.656356 Text en Copyright © 2021 López-Nevado, Docampo-Cordeiro, Ramos, Rodríguez-Pena, Gil-López, Sánchez-Ramón, Gil-Herrera, Díaz-Madroñero, Delgado-Martín, Morales-Pérez, Paz-Artal, Magerus, Rieux-Laucat and Allende https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
López-Nevado, Marta
Docampo-Cordeiro, Jorge
Ramos, José T.
Rodríguez-Pena, Rebeca
Gil-López, Celia
Sánchez-Ramón, Silvia
Gil-Herrera, Juana
Díaz-Madroñero, María J.
Delgado-Martín, María A.
Morales-Pérez, Pablo
Paz-Artal, Estela
Magerus, Aude
Rieux-Laucat, Frederic
Allende, Luis M.
Next Generation Sequencing for Detecting Somatic FAS Mutations in Patients With Autoimmune Lymphoproliferative Syndrome
title Next Generation Sequencing for Detecting Somatic FAS Mutations in Patients With Autoimmune Lymphoproliferative Syndrome
title_full Next Generation Sequencing for Detecting Somatic FAS Mutations in Patients With Autoimmune Lymphoproliferative Syndrome
title_fullStr Next Generation Sequencing for Detecting Somatic FAS Mutations in Patients With Autoimmune Lymphoproliferative Syndrome
title_full_unstemmed Next Generation Sequencing for Detecting Somatic FAS Mutations in Patients With Autoimmune Lymphoproliferative Syndrome
title_short Next Generation Sequencing for Detecting Somatic FAS Mutations in Patients With Autoimmune Lymphoproliferative Syndrome
title_sort next generation sequencing for detecting somatic fas mutations in patients with autoimmune lymphoproliferative syndrome
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117005/
https://www.ncbi.nlm.nih.gov/pubmed/33995372
http://dx.doi.org/10.3389/fimmu.2021.656356
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