先天性免疫错误(IEI)包括各种异质性遗传疾病,其中免疫系统的缺陷导致对感染和其他并发症的易感性增加。准确,IEI的及时诊断对于治疗计划和预后至关重要。在这项研究中,评估了临床外显子组测序(CES)诊断IEI的临床实用性。对于37名疑似症状的韩国患者,标志,或与IEI相关的实验室异常,进行涵盖4,894个基因(包括与IEI相关的基因)的CES。他们的临床诊断,临床特征,家族感染史,和实验室结果,以及检测到的变异,被审查了。随着CES,37例患者中有15例(40.5%)进行了IEI基因诊断。从IEI相关基因中检测到17种致病变异,BTK,UNC13D,STAT3,IL2RG,IL10RA,NRAS,SH2D1A,GATA2,TET2,PRF1和UBA1,其中四种变体以前未报道。其中,从GATA2,TET2和UBA1中鉴定出体细胞致病变异。此外,我们确定了两名由CES偶然诊断为IEI的患者,用于诊断未识别IEI患者的其他疾病。一起来看,这些结果证明了CES对IEI诊断的实用性,这有助于准确的诊断和适当的治疗。
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.