Mutations in XRCC4 cause primordial dwarfism without causing immunodeficiency

• Published in: Journal of human genetics Vol. 61; no. 8; pp. 679 - 685
• Main Authors: Saito, Shinta, Kurosawa, Aya, Adachi, Noritaka
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.08.2016
• Subjects: Animals; Disease Susceptibility; DNA End-Joining Repair; DNA Ligase ATP - metabolism; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Dwarfism, Pituitary - diagnosis; Dwarfism, Pituitary - genetics; Dwarfism, Pituitary - immunology; Enzyme Stability; Genetic Association Studies; Humans; Immunity - genetics; Immunologic Deficiency Syndromes; Mutation; Phenotype; Protein Binding
• ISSN: 1434-5161; 1435-232X
• DOI: 10.1038/jhg.2016.46

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.