Targeted Gene Sanger Sequencing Should Remain the First-Tier Genetic Test for Children Suspected to Have the Five Common X-Linked Inborn Errors of Immunity

• Main Authors: Koon Wing Chan, Chung Yin Wong, Daniel Leung, Xingtian Yang, Susanna F.S. Fok, Priscilla H.S. Mak, Lei Yao, Wen Ma, Huawei Mao, Xiaodong Zhao, Weiling Liang, Surjit Singh, Mohamed Ridha Barbouche, Jian Xin He, Li Ping Jiang, Woei Kang Liew, Minh Huong Thi Le, Dina Muktiarti, Fatima Johanna Santos-Ocampo, Reda Djidjik, Brahim Belaid, Intan Hakimah Ismail, Amir Hamzah Abdul Latiff, Way Seah Lee, Tong Xin Chen, Jinrong Liu, Runming Jin, Xiaochuan Wang, Yin Hsiu Chien, Hsin Hui Yu, Dinesh Raj, Revathi Raj, Jenifer Vaughan, Michael Urban, Sylvia van den Berg, Brian Eley, Anselm Chi Wai Lee, Mas Suhaila Isa, Elizabeth Y. Ang, Bee Wah Lee, Allen Eng Juh Yeoh, Lynette P. Shek, Nguyen Ngoc Quynh Le, Van Anh Thi Nguyen, Anh Phan Nguyen Lien, Regina D. Capulong, Joanne Michelle Mallillin, Jose Carlo Miguel M. Villanueva, Karol Anne B. Camonayan, Michelle De Vera, Roxanne J. Casis-Hao, Rommel Crisenio M. Lobo, Ruby Foronda, Vicky Wee Eng Binas, Soraya Boushaki, Nadia Kechout, Gun Phongsamart, Siriporn Wongwaree, Chamnanrua Jiratchaya, Mongkol Lao-Araya, Muthita Trakultivakorn, Narissara Suratannon, Orathai Jirapongsananuruk, Teerapol Chantveerawong, Wasu Kamchaisatian, Lee Lee Chan, Mia Tuang Koh, Ke Juin Wong, Siew Moy Fong, Meow Keong Thong, Zarina Abdul Latiff, Lokman Mohd Noh, Rajiva de Silva, Zineb Jouhadi, Khulood Al-Saad, Pandiarajan Vignesh, Ankur Kumar Jindal, Amit Rawat, Anju Gupta, Deepti Suri, Jing Yang, Elaine Yuen Ling Au, Janette Siu Yin Kwok, Siu Yuen Chan, Wayland Yuk Fun Hui, Gilbert T. Chua, Jaime Rosa Duque, Kai Ning Cheong, Patrick Chun Yin Chong, Marco Hok Kung Ho, Tsz Leung Lee, Wilfred Hing Sang Wong, Wanling Yang, Pamela P. Lee, Wenwei Tu, Xi Qiang Yang, Yu Lung Lau
• Other Authors: Siriraj Hospital
• Format: Article
• Published: 2022
• Subjects: Immunology and Microbiology; Medicine
• Online Access: https://repository.li.mahidol.ac.th/handle/123456789/74092
• Institution: Mahidol University

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.