Department of Paediatrics and Adolescent Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR, China.
Department of Immunology, Ministry of Education Key Laboratory of Major Diseases in Children, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.
Front Immunol. 2022 Jul 8;13:883446. doi: 10.3389/fimmu.2022.883446. eCollection 2022.
To address inborn errors of immunity (IEI) which were underdiagnosed in resource-limited regions, our centre developed and offered free genetic testing for the most common IEI by Sanger sequencing (SS) since 2001. With the establishment of The Asian Primary Immunodeficiency (APID) Network in 2009, the awareness and definitive diagnosis of IEI were further improved with collaboration among centres caring for IEI patients from East and Southeast Asia. We also started to use whole exome sequencing (WES) for undiagnosed cases and further extended our collaboration with centres from South Asia and Africa. With the increased use of Next Generation Sequencing (NGS), we have shifted our diagnostic practice from SS to WES. However, SS was still one of the key diagnostic tools for IEI for the past two decades. Our centre has performed 2,024 IEI SS genetic tests, with in-house protocol designed specifically for 84 genes, in 1,376 patients with 744 identified to have disease-causing mutations (54.1%). The high diagnostic rate after just one round of targeted gene SS for each of the 5 common IEI (X-linked agammaglobulinemia (XLA) 77.4%, Wiskott-Aldrich syndrome (WAS) 69.2%, X-linked chronic granulomatous disease (XCGD) 59.5%, X-linked severe combined immunodeficiency (XSCID) 51.1%, and X-linked hyper-IgM syndrome (HIGM1) 58.1%) demonstrated targeted gene SS should remain the first-tier genetic test for the 5 common X-linked IEI.
为了解决资源有限地区未被诊断出的先天性免疫缺陷（IEI）问题，自 2001 年以来，我们中心通过桑格测序（SS）免费为最常见的 IEI 提供基因检测。随着 2009 年亚洲原发性免疫缺陷（APID）网络的建立，通过东亚和东南亚关注 IEI 患者的中心之间的合作，进一步提高了对 IEI 的认识和明确诊断。我们还开始使用全外显子组测序（WES）来诊断未确诊的病例，并进一步扩大了与来自南亚和非洲的中心的合作。随着下一代测序（NGS）的广泛应用，我们已经将诊断实践从 SS 转移到 WES。然而，SS 仍然是过去 20 年来诊断 IEI 的关键工具之一。我们中心已经对 1376 名患者进行了 2024 次 IEI SS 基因测试，采用了专门针对 84 个基因的内部方案，其中 744 名患者被确定存在致病突变（54.1%）。对 5 种常见的 X 连锁 IEI（X 连锁无丙种球蛋白血症（XLA）77.4%、Wiskott-Aldrich 综合征（WAS）69.2%、X 连锁慢性肉芽肿病（XCGD）59.5%、X 连锁严重联合免疫缺陷（XSCID）51.1%和 X 连锁高免疫球蛋白 M 综合征（HIGM1）58.1%）进行一轮靶向基因 SS 检测，即可获得很高的诊断率，这表明靶向基因 SS 仍然应该是 5 种常见 X 连锁 IEI 的一线基因检测方法。
