Obeidat Loiy, Abu-Halaweh Marwan, Alzyoud Raed, Albsoul Eman, Zaravinos Apostolos
Department of Life Sciences, School of Sciences, European University Cyprus, Nicosia 2404, Cyprus.
Basic and Translational Research Center (BTCRC), Cancer Genetics, Genomics and Systems Biology Laboratory, Nicosia 2404, Cyprus.
Biomed Rep. 2024 Aug 30;21(5):160. doi: 10.3892/br.2024.1848. eCollection 2024 Nov.
Ιnborn errors of immunity (IEI) represents a heterogenous collection of >480 immune system anomalies, leading to severe infections, autoimmune disorders and malignancies. While these conditions are rare globally, their prevalence is notably higher in the Jordanian population, attributed to elevated rates of consanguinity. The intricate nature of IEI has driven the adoption of genomic technologies for the identification of associated genetic defects. In the present study, whole-exome sequencing was performed on nine Jordanian IEI patient samples, confirming germline single-nucleotide variations (SNVs) in 14 genes through Sanger sequencing. Of note, signal transducer and activator of transcription 1 (), elastase, neutrophil expressed () and interferon induced with helicase c domain 1 () harbored mutations that were previously unreported in the Jordanian IEI population. In addition, mutations in capping protein regulator and myosin 1 linker 2 (c.3683C>T), TNFα-induced protein 3-interacting protein 1 () (c.460C>G) and (c.1061T>C) were confirmed, marking their association with Jordanian IEI. For robustness, the genomic databases Ensemble, Genome AD and ClinVar were used to confirm the SNVs' associations with IEI. Kyoto Encyclopedia of Genes and Genomes pathway analysis also showed involvement of the IL-17 signaling pathway (including IL-17 receptor A), T-helper type 17 cell differentiation (including STAT1), the JAK-STAT signaling pathway (including STAT2 and tyrosine kinase 2), neutrophil extracellular trap formation (including ELANE), cocaine addiction [G protein signaling modulator 1 (GPSM1)] and cytokine-cytokine receptor interaction (IL-17 receptor C). In summary, exome sequencing identified a likely causative genetic defect in (PID-28), (PID-30) and (PID-33). The present findings reveal the association of novel , mutations with the clinical phenotype of the patients, as well as known mutations in , and , in addition to novel and mutations associated in the context of Jordanian IEI.
遗传性免疫缺陷病（IEI）是480多种免疫系统异常的异质性集合，可导致严重感染、自身免疫性疾病和恶性肿瘤。虽然这些疾病在全球范围内都很罕见，但在约旦人群中的患病率明显更高，这归因于近亲结婚率的上升。IEI的复杂性促使人们采用基因组技术来识别相关的基因缺陷。在本研究中，对9份约旦IEI患者样本进行了全外显子组测序，通过桑格测序在14个基因中确认了种系单核苷酸变异（SNV）。值得注意的是，信号转导和转录激活因子1（）、中性粒细胞表达的弹性蛋白酶（）和含解旋酶C结构域的干扰素诱导蛋白1（）存在先前在约旦IEI人群中未报告的突变。此外，还确认了帽蛋白调节因子和肌球蛋白1连接蛋白2（c.3683C>T）、TNFα诱导蛋白3相互作用蛋白1（）（c.460C>G）和（c.1061T>C）中的突变，表明它们与约旦IEI有关。为了确保结果的可靠性，使用了基因组数据库Ensemble、Genome AD和ClinVar来确认SNV与IEI的关联。京都基因与基因组百科全书通路分析还显示，IL-17信号通路（包括IL-17受体A）、辅助性T细胞17分化（包括STAT1）、JAK-STAT信号通路（包括STAT2和酪氨酸激酶2）、中性粒细胞胞外陷阱形成（包括ELANE）、可卡因成瘾[G蛋白信号调节剂1（GPSM1）]和细胞因子-细胞因子受体相互作用（IL-17受体C）均参与其中。总之，外显子组测序在（PID-28）、（PID-30）和（PID-33）中发现了可能的致病基因缺陷。本研究结果揭示了新的、突变与患者临床表型的关联，以及、和中的已知突变，此外还发现了与约旦IEI相关的新的和突变。
