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

• Published in: Frontiers in immunology Vol. 13; p. 883446
• Main Authors: Chan, Koon-Wing, Wong, Chung-Yin, Leung, Daniel, Yang, Xingtian, Fok, Susanna F. S., Mak, Priscilla H. S., Yao, Lei, Ma, Wen, Mao, Huawei, Zhao, Xiaodong, Liang, Weiling, Singh, Surjit, Barbouche, Mohamed-Ridha, He, Jian-Xin, Jiang, Li-Ping, Liew, Woei-Kang, Le, Minh Huong Thi, Muktiarti, Dina, Santos-Ocampo, Fatima Johanna, Djidjik, Reda, Belaid, Brahim, Ismail, Intan Hakimah, Abdul Latiff, Amir Hamzah, Lee, Way Seah, Chen, Tong-Xin, Liu, Jinrong, Jin, Runming, Wang, Xiaochuan, Chien, Yin Hsiu, Yu, Hsin-Hui, Raj, Dinesh, Raj, Revathi, Vaughan, Jenifer, Urban, Michael, Berg, Sylvia van den, Eley, Brian, Lee, Anselm Chi-Wai, Isa, Mas Suhaila, Ang, Elizabeth Y., Lee, Bee Wah, Yeoh, Allen Eng Juh, Shek, Lynette P., Quynh Le, Nguyen Ngoc, Nguyen, Van Anh Thi, Phan Nguyen Lien, Anh, Capulong, Regina D., Mallillin, Joanne Michelle, Villanueva, Jose Carlo Miguel M., Camonayan, Karol Anne B., Vera, Michelle De, Casis-Hao, Roxanne J., Lobo, Rommel Crisenio M., Foronda, Ruby, Binas, Vicky Wee Eng, Boushaki, Soraya, Kechout, Nadia, Phongsamart, Gun, Wongwaree, Siriporn, Jiratchaya, Chamnanrua, Lao-Araya, Mongkol, Trakultivakorn, Muthita, Suratannon, Narissara, Jirapongsananuruk, Orathai, Chantveerawong, Teerapol, Kamchaisatian, Wasu, Chan, Lee Lee, Koh, Mia Tuang, Wong, Ke Juin, Fong, Siew Moy, Thong, Meow-Keong, Latiff, Zarina Abdul, Noh, Lokman Mohd, Silva, Rajiva de, Jouhadi, Zineb, Al-Saad, Khulood, Vignesh, Pandiarajan, Jindal, Ankur Kumar, Rawat, Amit, Gupta, Anju, Suri, Deepti, Yang, Jing, Au, Elaine Yuen-Ling, Kwok, Janette Siu-Yin, Chan, Siu-Yuen, Hui, Wayland Yuk-Fun, Chua, Gilbert T., Duque, Jaime Rosa, Cheong, Kai-Ning, Chong, Patrick Chun Yin, Ho, Marco Hok Kung, Lee, Tsz-Leung, Wong, Wilfred Hing-Sang, Yang, Wanling, Lee, Pamela P., Tu, Wenwei, Yang, Xi-Qiang, Lau, Yu Lung
• Format: Journal Article
• Language: English
• Published: Frontiers Media S.A 08.07.2022
• Subjects: Immunology; inborn errors of immunity; next generation sequencing; primary immunodeficiency diseases; Sanger sequencing; targeted gene; whole exome sequencing
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2022.883446

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.