title: Mutations in XRCC4 cause primordial dwarfism without causing immunodeficiency.
abstract: In successive reports from 2014 to 2015, X-ray repair cross-complementing protein 4 (XRCC4) has been identified as a novel causative gene of primordial dwarfism. XRCC4 is indispensable for non-homologous end joining (NHEJ), the major pathway for repairing DNA double-strand breaks. As NHEJ is essential for V(D)J recombination during lymphocyte development, it is generally believed that abnormalities in XRCC4 cause severe combined immunodeficiency. Contrary to expectations, however, no overt immunodeficiency has been observed in patients with primordial dwarfism harboring XRCC4 mutations. Here, we describe the various XRCC4 mutations that lead to disease and discuss their impact on NHEJ and V(D)J recombination.
authors.affiliation: Graduate School of Nanobioscience, Yokohama City University, Yokohama, Japan.
authors.forename: Shinta
authors.initials: S
authors.lastname: Saito
authors.affiliation: Graduate School of Nanobioscience, Yokohama City University, Yokohama, Japan.|Faculty of Science and Technology, Gunma University, Kiryu, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Kurosawa
authors.affiliation: Graduate School of Nanobioscience, Yokohama City University, Yokohama, Japan.|Advanced Medical Research Center, Yokohama City University, Yokohama, Japan.
authors.forename: Noritaka
authors.initials: N
authors.lastname: Adachi
mesh_terms: D000818:Animals; D059766:DNA End-Joining Repair; D000072481:DNA Ligase ATP / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004198:Disease Susceptibility; D004393:Dwarfism, Pituitary / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology*; D004795:Enzyme Stability; D056726:Genetic Association Studies; D006801:Humans; D007109:Immunity / Q000235:genetics; D007153:Immunologic Deficiency Syndromes; D009154:Mutation; D010641:Phenotype; D011485:Protein Binding
chemical_list: D004268:DNA-Binding Proteins; C000607893:LIG4 protein, human; C101467:XRCC4 protein, human; D000072481:DNA Ligase ATP