Multiple genes have been implicated to have a role in asthma predisposition by association studies. Pediatric patients often manifest a more extensive form of this disease and a particularly severe disease course. It is likely that genetic predisposition could play a more substantial role in this group. This study is aimed at identifying the spectrum of rare and novel variation in known pediatric asthma susceptibility genes using whole exome sequencing analysis in nine individual cases of childhood onset allergic asthma. DNA samples from the nine children with a history of bronchial asthma diagnosis underwent whole exome sequencing on Ion Proton. For each patient, the entire complement of rare variation within strongly associated candidate genes was catalogued. The analysis showed 21 variants in the subjects, 13 had been previously identified, and 8 were novel. Also, among of which, nineteen were nonsynonymous and 2 were nonsense. With regard to the novel variants, the 2 nonsynonymous variants in the PRKG1 gene (PRKG1: p.C519W and PRKG1: p.G520W) were presented in 4 cases, and a nonsynonymous variant in the MAVS gene (MAVS: p.A45V) was identified in 3 cases. The variants we found in this study will enrich the variant spectrum and build up the database in the Saudi population. Novel eight variants were identified in the study which provides more evidence in the genetic susceptibility in asthma among Saudi children, providing a genetic screening map for the molecular genetic determinants of allergic disease in Saudi children, with the goal of reducing the impact of chronic diseases on the health and the economy. We believe that the advanced specified statistical filtration/annotation programs used in this study succeeded to release such results in a preliminary study, exploring the genetic map of that disease in Saudi children.

中文翻译：

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小儿哮喘的下一代外显子组测序鉴定候选基因中的罕见和新变体

关联研究表明多个基因在哮喘易感性中起作用。儿科患者通常表现出更广泛的这种疾病形式和特别严重的病程。遗传倾向可能在这个群体中发挥更重要的作用。本研究旨在利用全外显子组测序分析，在 9 例儿童过敏性哮喘病例中确定已知小儿哮喘易感基因的罕见和新变异谱。来自 9 名有支气管哮喘病史的儿童的 DNA 样本在 Ion Proton 上进行了全外显子组测序。对于每个患者，强烈关联的候选基因内的罕见变异的整个补充被编目。分析显示受试者中有 21 种变异，其中 13 种先前已被鉴定，和8是新颖的。另外，其中19个是非同义词，2个是胡说八道。关于新变体，2 个非同义变体在PRKG1基因（PRKG1 : p.C519W 和PRKG1 : p.G520W ）共出现 4 例，MAVS基因（MAVS: p.A45V) 在 3 例中被鉴定。我们在本研究中发现的变异将丰富变异谱并在沙特人群中建立数据库。研究发现了 8 个新的变异，为沙特儿童哮喘的遗传易感性提供了更多证据，为沙特儿童过敏性疾病的分子遗传决定因素提供了基因筛查图谱，目的是减少慢性病对儿童哮喘的影响。健康和经济。我们相信，本研究中使用的高级指定统计过滤/注释程序成功地在初步研究中发布了此类结果，探索了沙特儿童该疾病的遗传图谱。