title: Molecular diagnosis of severe combined immunodeficiency--identification of IL2RG, JAK3, IL7R, DCLRE1C, RAG1, and RAG2 mutations in a cohort of Chinese and Southeast Asian children.
abstract: Severe combined immunodeficiencies (SCID) are a group of rare inherited disorders with profound defects in T cell and B cell immunity. From 2005 to 2010, our unit performed testing for IL2RG, JAK3, IL7R, RAG1, RAG2, DCLRE1C, LIG4, AK2, and ZAP70 mutations in 42 Chinese and Southeast Asian infants with SCID adopting a candidate gene approach, based on patient's gender, immune phenotype, and inheritance pattern. Mutations were identified in 26 patients, including IL2RG (n = 19), IL7R (n = 2), JAK3 (n = 2), RAG1 (n = 1), RAG2 (n = 1), and DCLRE1C (n = 1). Among 12 patients who underwent hematopoietic stem cell transplantation, eight patients survived. Complications and morbidities during transplant period were significant, especially disseminated bacillus Calmette-Guérin disease which was often difficult to control. This is the first cohort study on SCID in the Chinese and Southeast Asian population, based on a multi-centered collaborative research network. The foremost issue is service provision for early detection, diagnosis, management, and definitive treatment for patients with SCID. National management guidelines for SCID should be established, and research into an efficient platform for genetic diagnosis is needed.
authors.affiliation: Department of Paediatrics and Adolescent Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
authors.forename: Pamela P W
authors.initials: PP
authors.lastname: Lee
authors.forename: Koon-Wing
authors.initials: KW
authors.lastname: Chan
authors.forename: Tong-Xin
authors.initials: TX
authors.lastname: Chen
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Jiang
authors.forename: Xiao-Chuan
authors.initials: XC
authors.lastname: Wang
authors.forename: Hua-Song
authors.initials: HS
authors.lastname: Zeng
authors.forename: Xiang-Yuan
authors.initials: XY
authors.lastname: Chen
authors.forename: Woei-Kang
authors.initials: WK
authors.lastname: Liew
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Kit-Man
authors.initials: KM
authors.lastname: Chu
authors.forename: Lee-Lee
authors.initials: LL
authors.lastname: Chan
authors.forename: Lynette
authors.initials: L
authors.lastname: Shek
authors.forename: Anselm C W
authors.initials: AC
authors.lastname: Lee
authors.forename: Hsin-Hui
authors.initials: HH
authors.lastname: Yu
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.forename: Chen-Guang
authors.initials: CG
authors.lastname: Xu
authors.forename: Geraldine
authors.initials: G
authors.lastname: Sultan-Ugdoracion
authors.forename: Zarina Abdul
authors.initials: ZA
authors.lastname: Latiff
authors.forename: Amir Hamzah Abdul
authors.initials: AH
authors.lastname: Latiff
authors.forename: Orathai
authors.initials: O
authors.lastname: Jirapongsananuruk
authors.forename: Marco H K
authors.initials: MH
authors.lastname: Ho
authors.forename: Tsz-Leung
authors.initials: TL
authors.lastname: Lee
authors.forename: Xi-Qiang
authors.initials: XQ
authors.lastname: Yang
authors.forename: Yu-Lung
authors.initials: YL
authors.lastname: Lau
mesh_terms: D000361:Agammaglobulinemia / Q000209:etiology / Q000276:immunology; D044466:Asian People / Q000235:genetics; D002675:Child, Preschool; D015331:Cohort Studies; D004268:DNA-Binding Proteins / Q000235:genetics; D004720:Endonucleases; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007239:Infections / Q000209:etiology; D053631:Interleukin Receptor Common gamma Subunit / Q000235:genetics; D053616:Janus Kinase 3 / Q000235:genetics; D007970:Leukopenia / Q000209:etiology / Q000276:immunology; D008297:Male; D009154:Mutation / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics; D020395:Receptors, Interleukin-7 / Q000235:genetics; D016511:Severe Combined Immunodeficiency / Q000150:complications / Q000175:diagnosis* / Q000235:genetics* / Q000628:therapy; D016896:Treatment Outcome
chemical_list: D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D053631:Interleukin Receptor Common gamma Subunit; D009687:Nuclear Proteins; C499311:RAG2 protein, human; D020395:Receptors, Interleukin-7; C064658:RAG-1 protein; D053616:Janus Kinase 3; C426344:DCLRE1C protein, human; D004720:Endonucleases