Clinical Utility of Whole Exome Sequencing and Targeted Panels for the Identification of Inborn Errors of Immunity in a Resource-Constrained Setting. Engelbrecht, C., Urban, M., Schoeman, M., Paarwater, B., van Coller, A., Abraham, D. R., Cornelissen, H., Glashoff, R., Esser, M., Möller, M., Kinnear, C., & Glanzmann, B. Frontiers in Immunology, 12:665621, 2021. doi abstract bibtex 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.
@article{engelbrecht_clinical_2021,
title = {Clinical {Utility} of {Whole} {Exome} {Sequencing} and {Targeted} {Panels} for the {Identification} of {Inborn} {Errors} of {Immunity} in a {Resource}-{Constrained} {Setting}},
volume = {12},
issn = {1664-3224},
doi = {10.3389/fimmu.2021.665621},
abstract = {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.},
language = {eng},
journal = {Frontiers in Immunology},
author = {Engelbrecht, Clair and Urban, Michael and Schoeman, Mardelle and Paarwater, Brandon and van Coller, Ansia and Abraham, Deepthi Raju and Cornelissen, Helena and Glashoff, Richard and Esser, Monika and Möller, Marlo and Kinnear, Craig and Glanzmann, Brigitte},
year = {2021},
pmid = {34093558},
pmcid = {PMC8176954},
keywords = {Adolescent, Child, Child, Preschool, Exome Sequencing, Family Health, Female, Genetic Diseases, Inborn, High-Throughput Nucleotide Sequencing, Humans, Immunity, Infant, Infant, Newborn, Male, Primary Immunodeficiency Diseases, South Africa, genetic variants, inborn errors of immunity, targeted sequencing, whole exome sequencing},
pages = {665621},
}
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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.","language":"eng","journal":"Frontiers in Immunology","author":[{"propositions":[],"lastnames":["Engelbrecht"],"firstnames":["Clair"],"suffixes":[]},{"propositions":[],"lastnames":["Urban"],"firstnames":["Michael"],"suffixes":[]},{"propositions":[],"lastnames":["Schoeman"],"firstnames":["Mardelle"],"suffixes":[]},{"propositions":[],"lastnames":["Paarwater"],"firstnames":["Brandon"],"suffixes":[]},{"propositions":["van"],"lastnames":["Coller"],"firstnames":["Ansia"],"suffixes":[]},{"propositions":[],"lastnames":["Abraham"],"firstnames":["Deepthi","Raju"],"suffixes":[]},{"propositions":[],"lastnames":["Cornelissen"],"firstnames":["Helena"],"suffixes":[]},{"propositions":[],"lastnames":["Glashoff"],"firstnames":["Richard"],"suffixes":[]},{"propositions":[],"lastnames":["Esser"],"firstnames":["Monika"],"suffixes":[]},{"propositions":[],"lastnames":["Möller"],"firstnames":["Marlo"],"suffixes":[]},{"propositions":[],"lastnames":["Kinnear"],"firstnames":["Craig"],"suffixes":[]},{"propositions":[],"lastnames":["Glanzmann"],"firstnames":["Brigitte"],"suffixes":[]}],"year":"2021","pmid":"34093558","pmcid":"PMC8176954","keywords":"Adolescent, Child, Child, Preschool, Exome Sequencing, Family Health, Female, Genetic Diseases, Inborn, High-Throughput Nucleotide Sequencing, Humans, Immunity, Infant, Infant, Newborn, Male, Primary Immunodeficiency Diseases, South Africa, genetic variants, inborn errors of immunity, targeted sequencing, whole exome sequencing","pages":"665621","bibtex":"@article{engelbrecht_clinical_2021,\n\ttitle = {Clinical {Utility} of {Whole} {Exome} {Sequencing} and {Targeted} {Panels} for the {Identification} of {Inborn} {Errors} of {Immunity} in a {Resource}-{Constrained} {Setting}},\n\tvolume = {12},\n\tissn = {1664-3224},\n\tdoi = {10.3389/fimmu.2021.665621},\n\tabstract = {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. 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