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Clinical Utility of Whole Exome Sequencing and Targeted Panels for the Identification of Inborn Errors of Immunity in a Resource-Constrained Setting

Primary immunodeficiency disorders (PIDs) are inborn errors of immunity (IEI) that cause immune system impairment. To date, more than 400 single-gene IEI have been well defined. The advent of next generation sequencing (NGS) technologies has improved clinical diagnosis and allowed for discovery of n...

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Autores principales: Engelbrecht, Clair, Urban, Michael, Schoeman, Mardelle, Paarwater, Brandon, van Coller, Ansia, Abraham, Deepthi Raju, Cornelissen, Helena, Glashoff, Richard, Esser, Monika, Möller, Marlo, Kinnear, Craig, Glanzmann, Brigitte
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176954/
https://www.ncbi.nlm.nih.gov/pubmed/34093558
http://dx.doi.org/10.3389/fimmu.2021.665621
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author Engelbrecht, Clair
Urban, Michael
Schoeman, Mardelle
Paarwater, Brandon
van Coller, Ansia
Abraham, Deepthi Raju
Cornelissen, Helena
Glashoff, Richard
Esser, Monika
Möller, Marlo
Kinnear, Craig
Glanzmann, Brigitte
author_facet Engelbrecht, Clair
Urban, Michael
Schoeman, Mardelle
Paarwater, Brandon
van Coller, Ansia
Abraham, Deepthi Raju
Cornelissen, Helena
Glashoff, Richard
Esser, Monika
Möller, Marlo
Kinnear, Craig
Glanzmann, Brigitte
author_sort Engelbrecht, Clair
collection PubMed
description Primary immunodeficiency disorders (PIDs) are inborn errors of immunity (IEI) that cause immune system impairment. To date, more than 400 single-gene IEI have been well defined. The advent of next generation sequencing (NGS) technologies has improved clinical diagnosis and allowed for discovery of novel genes and variants associated with IEI. Molecular diagnosis provides clear clinical benefits for patients by altering management, enabling access to certain treatments and facilitates genetic counselling. Here we report on an 8-year experience using two different NGS technologies, namely research-based WES and targeted gene panels, in patients with suspected IEI in the South African healthcare system. A total of 52 patients’ had WES only, 26 had a targeted gene panel only, and 2 had both panel and WES. Overall, a molecular diagnosis was achieved in 30% (24/80) of patients. Clinical management was significantly altered in 67% of patients following molecular results. All 24 families with a molecular diagnosis received more accurate genetic counselling and family cascade testing. Results highlight the clinical value of expanded genetic testing in IEI and its relevance to understanding the genetic and clinical spectrum of the IEI-related disorders in Africa. Detection rates under 40% illustrate the complexity and heterogeneity of these disorders, especially in an African population, thus highlighting the need for expanded genomic testing and research to further elucidate this.
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spelling pubmed-81769542021-06-05 Clinical Utility of Whole Exome Sequencing and Targeted Panels for the Identification of Inborn Errors of Immunity in a Resource-Constrained Setting Engelbrecht, Clair Urban, Michael Schoeman, Mardelle Paarwater, Brandon van Coller, Ansia Abraham, Deepthi Raju Cornelissen, Helena Glashoff, Richard Esser, Monika Möller, Marlo Kinnear, Craig Glanzmann, Brigitte Front Immunol Immunology Primary immunodeficiency disorders (PIDs) are inborn errors of immunity (IEI) that cause immune system impairment. To date, more than 400 single-gene IEI have been well defined. The advent of next generation sequencing (NGS) technologies has improved clinical diagnosis and allowed for discovery of novel genes and variants associated with IEI. Molecular diagnosis provides clear clinical benefits for patients by altering management, enabling access to certain treatments and facilitates genetic counselling. Here we report on an 8-year experience using two different NGS technologies, namely research-based WES and targeted gene panels, in patients with suspected IEI in the South African healthcare system. A total of 52 patients’ had WES only, 26 had a targeted gene panel only, and 2 had both panel and WES. Overall, a molecular diagnosis was achieved in 30% (24/80) of patients. Clinical management was significantly altered in 67% of patients following molecular results. All 24 families with a molecular diagnosis received more accurate genetic counselling and family cascade testing. Results highlight the clinical value of expanded genetic testing in IEI and its relevance to understanding the genetic and clinical spectrum of the IEI-related disorders in Africa. Detection rates under 40% illustrate the complexity and heterogeneity of these disorders, especially in an African population, thus highlighting the need for expanded genomic testing and research to further elucidate this. Frontiers Media S.A. 2021-05-21 /pmc/articles/PMC8176954/ /pubmed/34093558 http://dx.doi.org/10.3389/fimmu.2021.665621 Text en Copyright © 2021 Engelbrecht, Urban, Schoeman, Paarwater, van Coller, Abraham, Cornelissen, Glashoff, Esser, Möller, Kinnear and Glanzmann 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
Engelbrecht, Clair
Urban, Michael
Schoeman, Mardelle
Paarwater, Brandon
van Coller, Ansia
Abraham, Deepthi Raju
Cornelissen, Helena
Glashoff, Richard
Esser, Monika
Möller, Marlo
Kinnear, Craig
Glanzmann, Brigitte
Clinical Utility of Whole Exome Sequencing and Targeted Panels for the Identification of Inborn Errors of Immunity in a Resource-Constrained Setting
title Clinical Utility of Whole Exome Sequencing and Targeted Panels for the Identification of Inborn Errors of Immunity in a Resource-Constrained Setting
title_full Clinical Utility of Whole Exome Sequencing and Targeted Panels for the Identification of Inborn Errors of Immunity in a Resource-Constrained Setting
title_fullStr Clinical Utility of Whole Exome Sequencing and Targeted Panels for the Identification of Inborn Errors of Immunity in a Resource-Constrained Setting
title_full_unstemmed Clinical Utility of Whole Exome Sequencing and Targeted Panels for the Identification of Inborn Errors of Immunity in a Resource-Constrained Setting
title_short Clinical Utility of Whole Exome Sequencing and Targeted Panels for the Identification of Inborn Errors of Immunity in a Resource-Constrained Setting
title_sort clinical utility of whole exome sequencing and targeted panels for the identification of inborn errors of immunity in a resource-constrained setting
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176954/
https://www.ncbi.nlm.nih.gov/pubmed/34093558
http://dx.doi.org/10.3389/fimmu.2021.665621
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