Genetic diagnosis of inborn errors of immunity using clinical exome sequencing

Frontiers in Immunology

Immunology

Dongju Won¹  Youn Keong Cho¹  Saeam Shin¹  Soon Sung Kwon¹  Jong Rak Choi²  Seung-Tae Lee²  Seungmin Hahn³  Jong Gyun Ahn⁴  Ji-Man Kang⁴  Jiyoung Oh⁵ 

[1] Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea;Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea;Dxome, Seoul, Republic of Korea;Department of Pediatric Hemato-oncology, Yonsei Cancer Center, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea;Department of Pediatrics, Severance Children’s Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea;Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, Republic of Korea;Division of Clinical Genetics, Department of Pediatrics, Severance Children’s Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea;

关键词: inborn errors of immunity;    next generation sequencing;    clinical exome sequencing;    genetic diagnosis;    somatic variant;    incidental finding;   

DOI  :  10.3389/fimmu.2023.1178582

 received in 2023-03-03, accepted in 2023-05-15,  发布年份 2023

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

Unknown   
Copyright © 2023 Kwon, Cho, Hahn, Oh, Won, Shin, Kang, Ahn, Lee and Choi