title: Molecular and immunological characterization of DNA ligase IV deficiency.
abstract: DNA ligase IV (LIG4) deficiency is an extremely rare autosomal recessive primary immunodeficiency disease caused by the LIG4 mutation. To date, fewer than 30 cases of patients have been reported worldwide. No reversion mutations have been previously identified in LIG4. This study enrolled seven Chinese patients with LIG4 deficiency who presented with combined immunodeficiency, microcephaly, and growth retardation. One patient (P1) acquired non-Hodgkin lymphoma. Four patients had impaired T cell proliferation function and skewed T cell receptor diversity. Five novel mutations in LIG4 and a potential hotspot mutation (c.833G>T; p.R278L) in the Chinese population were identified. TA cloning analysis of T cells, NK cells, granulocytes, and oral mucosa cells in P6 revealed wild-type clones and clones that contained both maternally and paternally inherited mutations, indicating possible somatic reversion which need further investigation since no functional or protein assays were possible for all the patients died and no cell lines were available.
authors.affiliation: Division of Immunology, Children's Hospital of Chongqing Medical University, China.
authors.forename: Jinqiu
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Division of Immunology, Children's Hospital of Chongqing Medical University, China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Tang
authors.affiliation: Division of Immunology, Children's Hospital of Chongqing Medical University, China; Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, China; Research Center for Immunologic and Infectious diseases, Children's Hospital of Chongqing Medical University, Chongqing 400014, China. Electronic address: anyf82@aliyun.com.
authors.forename: Yunfei
authors.initials: Y
authors.lastname: An
authors.affiliation: Division of Immunology, Children's Hospital of Chongqing Medical University, China.
authors.forename: Maozhi
authors.initials: M
authors.lastname: Tang
authors.affiliation: Division of Immunology, Children's Hospital of Chongqing Medical University, China.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Wu
authors.affiliation: Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Qin
authors.affiliation: Division of Immunology, Children's Hospital of Chongqing Medical University, China; Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, China; Research Center for Immunologic and Infectious diseases, Children's Hospital of Chongqing Medical University, Chongqing 400014, China. Electronic address: zhaoxd@cqmu.edu.cn.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhao
mesh_terms: D044466:Asian People; D049109:Cell Proliferation / Q000235:genetics; D002675:Child, Preschool; D002681:China; D000072481:DNA Ligase ATP; D011088:DNA Ligases / Q000172:deficiency / Q000235:genetics*; D005260:Female; D005838:Genotype; D006098:Granulocytes / Q000276:immunology / Q000378:metabolism; D006130:Growth Disorders / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics* / Q000276:immunology; D007223:Infant; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics* / Q000276:immunology; D008297:Male; D008831:Microcephaly / Q000235:genetics* / Q000276:immunology; D009154:Mutation; D010641:Phenotype; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D013577:Syndrome; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: C000607893:LIG4 protein, human; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011088:DNA Ligases; D000072481:DNA Ligase ATP
keywords: Immunodeficiency; LIG4; NHEJ; Somatic reversion