Genetic diagnosis of inborn errors of immunity using clinical exome sequencing
Inborn errors of immunity (IEI) include a variety of heterogeneous genetic disorders in which defects in the immune system lead to an increased susceptibility to infections and other complications. Accurate, prompt diagnosis of IEI is crucial for treatment plan and prognostication. In this study, cl...
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| Format: | Article |
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Frontiers Media S.A.
2023-05-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1178582/full |
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| author | Soon Sung Kwon Youn Keong Cho Seungmin Hahn Jiyoung Oh Dongju Won Saeam Shin Ji-Man Kang Ji-Man Kang Jong Gyun Ahn Jong Gyun Ahn Seung-Tae Lee Seung-Tae Lee Jong Rak Choi Jong Rak Choi |
| author_facet | Soon Sung Kwon Youn Keong Cho Seungmin Hahn Jiyoung Oh Dongju Won Saeam Shin Ji-Man Kang Ji-Man Kang Jong Gyun Ahn Jong Gyun Ahn Seung-Tae Lee Seung-Tae Lee Jong Rak Choi Jong Rak Choi |
| author_sort | Soon Sung Kwon |
| collection | DOAJ |
| description | Inborn errors of immunity (IEI) include a variety of heterogeneous genetic disorders in which defects in the immune system lead to an increased susceptibility to infections and other complications. Accurate, prompt diagnosis of IEI is crucial for treatment plan and prognostication. In this study, clinical utility of clinical exome sequencing (CES) for diagnosis of IEI was evaluated. For 37 Korean patients with suspected symptoms, signs, or laboratory abnormalities associated with IEI, CES that covers 4,894 genes including genes related to IEI was performed. Their clinical diagnosis, clinical characteristics, family history of infection, and laboratory results, as well as detected variants, were reviewed. With CES, genetic diagnosis of IEI was made in 15 out of 37 patients (40.5%). Seventeen pathogenic variants were detected from IEI-related genes, BTK, UNC13D, STAT3, IL2RG, IL10RA, NRAS, SH2D1A, GATA2, TET2, PRF1, and UBA1, of which four variants were previously unreported. Among them, somatic causative variants were identified from GATA2, TET2, and UBA1. In addition, we identified two patients incidentally diagnosed IEI by CES, which was performed to diagnose other diseases of patients with unrecognized IEI. Taken together, these results demonstrate the utility of CES for the diagnosis of IEI, which contributes to accurate diagnosis and proper treatments. |
| first_indexed | 2024-03-13T04:32:56Z |
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| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-13T04:32:56Z |
| publishDate | 2023-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-3bd1a2f4a4784323a6bd6c1c3eb0f0ba2023-06-19T08:08:00ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-05-011410.3389/fimmu.2023.11785821178582Genetic diagnosis of inborn errors of immunity using clinical exome sequencingSoon Sung Kwon0Youn Keong Cho1Seungmin Hahn2Jiyoung Oh3Dongju Won4Saeam Shin5Ji-Man Kang6Ji-Man Kang7Jong Gyun Ahn8Jong Gyun Ahn9Seung-Tae Lee10Seung-Tae Lee11Jong Rak Choi12Jong Rak Choi13Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Republic of KoreaDepartment of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Republic of KoreaDepartment of Pediatric Hemato-oncology, Yonsei Cancer Center, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of KoreaDivision of Clinical Genetics, Department of Pediatrics, Severance Children’s Hospital, Yonsei University College of Medicine, Seoul, Republic of KoreaDepartment of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Republic of KoreaDepartment of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Republic of KoreaDepartment of Pediatrics, Severance Children’s Hospital, Yonsei University College of Medicine, Seoul, Republic of KoreaInstitute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, Republic of KoreaDepartment of Pediatrics, Severance Children’s Hospital, Yonsei University College of Medicine, Seoul, Republic of KoreaInstitute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, Republic of KoreaDepartment of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Republic of KoreaDxome, Seoul, Republic of KoreaDepartment of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Republic of KoreaDxome, Seoul, Republic of KoreaInborn errors of immunity (IEI) include a variety of heterogeneous genetic disorders in which defects in the immune system lead to an increased susceptibility to infections and other complications. Accurate, prompt diagnosis of IEI is crucial for treatment plan and prognostication. In this study, clinical utility of clinical exome sequencing (CES) for diagnosis of IEI was evaluated. For 37 Korean patients with suspected symptoms, signs, or laboratory abnormalities associated with IEI, CES that covers 4,894 genes including genes related to IEI was performed. Their clinical diagnosis, clinical characteristics, family history of infection, and laboratory results, as well as detected variants, were reviewed. With CES, genetic diagnosis of IEI was made in 15 out of 37 patients (40.5%). Seventeen pathogenic variants were detected from IEI-related genes, BTK, UNC13D, STAT3, IL2RG, IL10RA, NRAS, SH2D1A, GATA2, TET2, PRF1, and UBA1, of which four variants were previously unreported. Among them, somatic causative variants were identified from GATA2, TET2, and UBA1. In addition, we identified two patients incidentally diagnosed IEI by CES, which was performed to diagnose other diseases of patients with unrecognized IEI. Taken together, these results demonstrate the utility of CES for the diagnosis of IEI, which contributes to accurate diagnosis and proper treatments.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1178582/fullinborn errors of immunitynext generation sequencingclinical exome sequencinggenetic diagnosissomatic variantincidental finding |
| spellingShingle | Soon Sung Kwon Youn Keong Cho Seungmin Hahn Jiyoung Oh Dongju Won Saeam Shin Ji-Man Kang Ji-Man Kang Jong Gyun Ahn Jong Gyun Ahn Seung-Tae Lee Seung-Tae Lee Jong Rak Choi Jong Rak Choi Genetic diagnosis of inborn errors of immunity using clinical exome sequencing Frontiers in Immunology inborn errors of immunity next generation sequencing clinical exome sequencing genetic diagnosis somatic variant incidental finding |
| title | Genetic diagnosis of inborn errors of immunity using clinical exome sequencing |
| title_full | Genetic diagnosis of inborn errors of immunity using clinical exome sequencing |
| title_fullStr | Genetic diagnosis of inborn errors of immunity using clinical exome sequencing |
| title_full_unstemmed | Genetic diagnosis of inborn errors of immunity using clinical exome sequencing |
| title_short | Genetic diagnosis of inborn errors of immunity using clinical exome sequencing |
| title_sort | genetic diagnosis of inborn errors of immunity using clinical exome sequencing |
| topic | inborn errors of immunity next generation sequencing clinical exome sequencing genetic diagnosis somatic variant incidental finding |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1178582/full |
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