Purpose: The goal of this study is to characterize the genomic landscape of pediatric rheumatological disorders in the Middle East, and to assess the clinical utility of genetic findings in this group of patients. Methods: Seventy-one pediatric patients were clinically and genetically assessed for a spectrum of rheumatology-related disease at the only dedicated tertiary childrens hospital in the United Arab Emirates. Clinical genomic investigations included genotyping, NGS-based gene panels, whole exome sequencing, along with rapid sequencing in the intensive care unit (ICU) and urgent setting. Results: The overall positive yield was 46.5% (18.2%-66.7%), while dual diagnoses were made in 2 cases (6%). Although the majority (21/33, 64%) of positive findings involved the MEFV gene, the remaining (12/33, 36%) alterations were attributed to eleven other genes/loci. Copy number variants contributed substantially (5/33, 15.2%) to the overall diagnostic yield. Sequencing-based testing, specifically rapid sequencing, had high positive rate and delivered timely results. Genetic findings guided clinical management plans and interventions in most cases (27/33, 81.8%). We highlight unique findings and provide additional evidence that heterozygous loss of function of the IFIH1 gene increases susceptibility to recurrent fevers. Conclusion: Our study highlights the importance of comprehensive genomic investigations in patients with pediatric rheumatological disorders.

中文翻译：

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中东地区小儿风湿病的基因组景观

目的：本研究的目的是表征中东地区儿童风湿病的基因组情况，并评估该组患者的遗传发现的临床应用。方法：在阿拉伯联合酋长国唯一的专科三级儿童医院，对71名儿科患者进行了临床和遗传学方面的风湿病相关疾病谱评估。临床基因组研究包括基因分型，基于NGS的基因检测，全外显子组测序以及重症监护病房（ICU）和紧急情况下的快速测序。结果：总体阳性率为46.5％（18.2％-66.7％），而双重诊断为2例（6％）。尽管大多数阳性结果（21/33，64％）涉及MEFV基因，其余（12/33，36％的变化归因于其他11个基因/基因座。拷贝数变体对总诊断产率贡献显着（5 / 33，15.2％）。基于测序的测试，特别是快速测序，具有很高的阳性率，并能及时提供结果。遗传结果指导大多数病例的临床治疗计划和干预措施（27 / 33，81.8％）。我们强调独特的发现，并提供额外的证据，即IFIH1基因功能的杂合性丧失会增加对反复发烧的敏感性。结论：我们的研究强调了小儿风湿病患者全面基因组研究的重要性。阳性率高，并能及时取得结果。遗传结果指导大多数病例的临床治疗计划和干预措施（27 / 33，81.8％）。我们强调独特的发现，并提供额外的证据，即IFIH1基因功能的杂合性丧失会增加对反复发烧的敏感性。结论：我们的研究强调了小儿风湿病患者全面基因组研究的重要性。阳性率高，并能及时取得结果。遗传结果指导大多数病例的临床治疗计划和干预措施（27 / 33，81.8％）。我们强调独特的发现，并提供额外的证据，即IFIH1基因功能的杂合性丧失会增加对反复发烧的敏感性。结论：我们的研究强调了小儿风湿病患者全面基因组研究的重要性。