Clinical Pathology Department, Faculty of Medicine, Cairo University, Cairo, Egypt.
Pediatrics Department, Faculty of Medicine, Cairo University, Cairo, Egypt.
J Clin Immunol. 2022 Jul;42(5):1051-1070. doi: 10.1007/s10875-022-01272-y. Epub 2022 Apr 28.
Inborn errors of immunity (IEI) are a group of heterogeneous disorders with geographic and ethnic diversities. Although IEI are common in Egypt, genetic diagnosis is limited due to financial restrictions. This study aims to characterize the genetic spectrum of IEI patients in Egypt and highlights the adaptation of the molecular diagnostic methods to a resource-limited setting.
Genetic material from 504 patients was studied, and proper diagnosis was achieved in 282 patients from 246 families. Mutational analysis was done by Sanger sequencing, next-generation sequencing (NGS) targeting customized genes panels, and whole-exome sequencing (WES) according to the patients' phenotypes and availability of genetic testing.
A total of 194 variants involving 72 different genes were detected with RAG1/2 genes being the most encountered followed by DOCK8, CYBA, LRBA, NCF1, and JAK3. Autosomal recessive (AR) inheritance was detected in 233/282 patients (82.6%), X-linked (XL) recessive inheritance in 32/282 patients (11.3%), and autosomal dominant (AD) inheritance in 18/282 patients (6.4%), reflecting the impact of consanguineous marriages on the prevalence of different modes of inheritance and the distribution of the various IEI disorders.
The study showed that a combination of Sanger sequencing in selected patients associated with targeted NGS or WES in other patients is an effective diagnostic strategy for IEI diagnosis in countries with limited diagnostic resources. Molecular testing can be used to validate other nonexpensive laboratory techniques that help to reach definitive diagnosis and help in genetic counseling and taking proper therapeutic decisions including stem cell transplantation or gene therapy.
先天性免疫缺陷（IEI）是一组具有地理和种族多样性的异质性疾病。尽管 IEI 在埃及很常见，但由于资金限制，遗传诊断受到限制。本研究旨在描述埃及 IEI 患者的遗传谱，并强调将分子诊断方法适应当地资源有限的环境。
研究了 504 名患者的遗传物质，从 246 个家庭的 282 名患者中获得了适当的诊断。通过 Sanger 测序、靶向定制基因面板的下一代测序（NGS）和根据患者表型和遗传检测可用性进行全外显子组测序（WES）进行突变分析。
共检测到涉及 72 个不同基因的 194 个变异，其中 RAG1/2 基因最常见，其次是 DOCK8、CYBA、LRBA、NCF1 和 JAK3。在 282 名患者中，233 名（82.6%）为常染色体隐性遗传（AR），32 名（11.3%）为 X 连锁隐性遗传（XL），18 名（6.4%）为常染色体显性遗传（AD），这反映了近亲结婚对不同遗传模式的流行和各种 IEI 疾病的分布的影响。
该研究表明，在诊断资源有限的国家，对选定患者进行 Sanger 测序与对其他患者进行靶向 NGS 或 WES 的结合是 IEI 诊断的有效诊断策略。分子检测可用于验证其他有助于明确诊断的非昂贵实验室技术，并有助于遗传咨询和采取适当的治疗决策，包括干细胞移植或基因治疗。
