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The genomic landscape of pediatric rheumatology disorders in the Middle East
Human Mutation ( IF 3.3 ) Pub Date : 2021-01-13 , DOI: 10.1002/humu.24165 Basil M Fathalla 1 , Ali Alsarhan 2 , Samina Afzal 3 , Maha El Naofal 4 , Ahmad Abou Tayoun 4, 5
Human Mutation ( IF 3.3 ) Pub Date : 2021-01-13 , DOI: 10.1002/humu.24165 Basil M Fathalla 1 , Ali Alsarhan 2 , Samina Afzal 3 , Maha El Naofal 4 , Ahmad Abou Tayoun 4, 5
Affiliation
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The landscape and clinical utility of comprehensive genomic investigations for a wide range of pediatric rheumatic disorders have not been fully characterized in the Middle East. Here, 71 pediatric patients, of diverse Arab origins, were clinically and genetically assessed for a spectrum of rheumatology‐related diseases at the only dedicated tertiary children's hospital in the United Arab Emirates. Clinical genomic investigations included mainly (76%) next‐generation sequencing‐based gene panels and whole‐exome sequencing, along with rapid sequencing in the intensive care unit and urgent setting. The overall positive yield was 46.5%, whereas dual diagnoses were made in two cases (3%). Although the majority (21/33, 64%) of positive findings involved the MEFV gene, the remaining (12/33, 36%) alterations were attributed to 11 other genes/loci. Copy number variants (CNVs) contributed substantially (5/33, 15.2%) to the overall diagnostic yield. Sequencing‐based testing, specifically rapid sequencing, had a 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. Our study provides new insights into the pathogenic variation landscape in pediatric rheumatic disorders.
中文翻译：
中东小儿风湿病的基因组图谱
中东地区尚未完全描述针对各种儿科风湿性疾病的综合基因组研究的前景和临床效用。在这里，71 名来自不同阿拉伯血统的儿科患者在阿拉伯联合酋长国唯一一家专门的三级儿童医院接受了一系列风湿病相关疾病的临床和基因评估。临床基因组研究主要包括 (76%) 基于下一代测序的基因组和全外显子组测序，以及重症监护室和紧急情况下的快速测序。总体阳性率为 46.5%，而双重诊断为 2 例 (3%)。尽管大多数 (21/33, 64%) 的阳性结果涉及MEFV基因，其余 (12/33, 36%) 改变归因于 11 个其他基因/位点。拷贝数变异 (CNV) 对总体诊断率的贡献很大 (5/33, 15.2%)。基于测序的检测，特别是快速测序，阳性率高，结果及时。在大多数情况下，遗传发现指导了临床管理计划和干预措施（27/33，81.8%）。我们强调了独特的发现并提供了额外的证据，表明IFIH1基因的杂合功能丧失增加了对反复发烧的易感性。我们的研究为小儿风湿性疾病的致病变异格局提供了新的见解。
更新日期：2021-01-13
中文翻译：
中东小儿风湿病的基因组图谱
中东地区尚未完全描述针对各种儿科风湿性疾病的综合基因组研究的前景和临床效用。在这里，71 名来自不同阿拉伯血统的儿科患者在阿拉伯联合酋长国唯一一家专门的三级儿童医院接受了一系列风湿病相关疾病的临床和基因评估。临床基因组研究主要包括 (76%) 基于下一代测序的基因组和全外显子组测序，以及重症监护室和紧急情况下的快速测序。总体阳性率为 46.5%，而双重诊断为 2 例 (3%)。尽管大多数 (21/33, 64%) 的阳性结果涉及MEFV基因，其余 (12/33, 36%) 改变归因于 11 个其他基因/位点。拷贝数变异 (CNV) 对总体诊断率的贡献很大 (5/33, 15.2%)。基于测序的检测，特别是快速测序，阳性率高，结果及时。在大多数情况下，遗传发现指导了临床管理计划和干预措施（27/33，81.8%）。我们强调了独特的发现并提供了额外的证据，表明IFIH1基因的杂合功能丧失增加了对反复发烧的易感性。我们的研究为小儿风湿性疾病的致病变异格局提供了新的见解。
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