Severe combined immunodeficiency (SCID) has a diverse genetic aetiology, where a clinical phenotype, caused by single and/or multiple gene variants, can give rise to multiple presentations. The advent of next‐generation sequencing (NGS) has recently enabled rapid identification of the molecular aetiology of SCID, which is crucial for prognosis and treatment strategies. We sought to identify the genetic aetiology of various phenotypes of SCIDs and assessed both clinical and immunologic characteristics associated with gene variants. An amplicon‐based targeted NGS panel, which contained 18 most common SCID‐related genes, was contumely made to screen the patients (n = 38) with typical SCID, atypical SCID or OMENN syndrome. Allelic segregations were confirmed for the detected gene variants within the families. In total, 24 disease‐causing variants (17 known and 7 novel) were identified in 23 patients in 9 different SCID genes: RAG1 (n = 5), RAG2 (n = 2), ADA (n = 3), DCLRE1C (n = 2), NHEJ1 (n = 2), CD3E (n = 2), IL2RG (n = 3), JAK3 (n = 4) and IL7R (n = 1). The overall success rate of our custom‐made NGS panel was 60% (39.3% for NK+ SCID and 100% for NK− SCID). Incidence of autosomal‐recessive inherited genes is more frequently found in our cohort than the previously reported populations probably due to the high consanguineous marriages in Turkey. In conclusion, the custom‐made sequencing panel was able to identify and confirm the previously known and novel disease‐causing variants with high accuracy.

中文翻译：

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土耳其重症联合免疫缺陷患者的突变情况

严重联合免疫缺陷 (SCID) 具有多种遗传病因，其中由单个和/或多个基因变异引起的临床表型可引起多种表现。近年来，新一代测序 (NGS) 的出现使得能够快速识别 SCID 的分子病因，这对预后和治疗策略至关重要。我们试图确定 SCID 各种表型的遗传病因，并评估与基因变异相关的临床和免疫学特征。一个基于扩增子的靶向 NGS 面板包含 18 个最常见的 SCID 相关基因，用于筛选具有典型 SCID、非典型 SCID 或 OMENN 综合征的患者（n = 38）。确认了家族内检测到的基因变异的等位基因分离。总共，在 23 名患者的 9 种不同 SCID 基因中鉴定出 24 种致病变异（17 种已知和 7 种新变异）：RAG1 (n = 5)、RAG2 (n = 2)、ADA (n = 3)、DCLRE1C (n = 2) 、NHEJ1 (n = 2)、CD3E (n = 2)、IL2RG (n = 3)、JAK3 (n = 4) 和 IL7R (n = 1)。我们定制的 NGS panel 的总体成功率为 60%（NK+ SCID 为 39.3%，NK− SCID 为 100%）。常染色体隐性遗传基因的发生率在我们的队列中比之前报道的人群中更常见，这可能是由于土耳其的近亲结婚率高。总之，定制的测序面板能够以高精度识别和确认先前已知的和新的致病变异。IL2RG (n = 3)、JAK3 (n = 4) 和 IL7R (n = 1)。我们定制的 NGS panel 的总体成功率为 60%（NK+ SCID 为 39.3%，NK− SCID 为 100%）。常染色体隐性遗传基因的发生率在我们的队列中比之前报道的人群中更常见，这可能是由于土耳其的近亲结婚率高。总之，定制的测序面板能够以高精度识别和确认先前已知的和新的致病变异。IL2RG (n = 3)、JAK3 (n = 4) 和 IL7R (n = 1)。我们定制的 NGS panel 的总体成功率为 60%（NK+ SCID 为 39.3%，NK− SCID 为 100%）。常染色体隐性遗传基因的发生率在我们的队列中比之前报道的人群中更常见，这可能是由于土耳其的近亲结婚率高。总之，定制的测序面板能够以高精度识别和确认先前已知的和新的致病变异。