| H00092 | |
| H number | H00092 |
| Name | T-B-Severe combined immunodeficiency |
| Description | Severe combined immunodeficiency (SCID) comprises a heterogeneous group of monogenic disorders that result in early-onset severe infections by a range of pathogens (such as bacteria, viruses and fungi). Typically, patients with SCID have a severe defect in T-cell differentiation, along with direct or indirect impairment of B-cell development and function. Adenosine deaminase (ADA) deficiency accounts for about half of the autosomal recessive forms of SCIDs. It is one of the most severe immunodeficiencies and is associated with severe depletion of B cells, T cells, and NK cells. V(D)J- recombination deficiency caused by defects in recombinase-activating gene 1 (RAG1), RAG2 and Artemis (DCLRE1C) leads to a T-B-SCID phenotype that is characterized by an arrest of B- and T-cell maturation at the stage of pro-B and pre-T cells, respectively, whereas natural killer (NK)-cell maturation is not affected. V(D)J recombination generates the diversity of B- and T-cell primary immune repertoires. |
| Category | Primary immunodeficiency |
| Network | nt06506(H00092) Double-strand break repair |
| Gene | ADA [HSA:100] [KO:K01488] RAG1 [HSA:5896] [KO:K10628] RAG2 [HSA:5897] [KO:K10988] DCLRE1C [HSA:64421] [KO:K10887] AK2 [HSA:204] [KO:K00939] PRKDC [HSA:5591] [KO:K06642] |
| Pathogen | - |
| Env factor | - |
| Carcinogen | - |
| Drug | - |
| Comment | - |
| Other DBs | ICD-11: 4A01.10 ICD-10: D81 MeSH: C563440 OMIM: 102700 601457 602450 267500 615966 |
| Reference | PMID:14647478 AUTHORS de Villartay JP, Fischer A, Durandy A. TITLE The mechanisms of immune diversification and their disorders. JOURNAL Nat Rev Immunol 3:962-72 (2003) DOI:10.1038/nri1247 PMID:9737224 AUTHORS Ten RM. TITLE Primary immunodeficiencies. JOURNAL Mayo Clin Proc 73:865-72 (1998) DOI:10.4065/73.9.865 PMID:26482257 AUTHORS Picard C, Al-Herz W, Bousfiha A, Casanova JL, Chatila T, Conley ME, Cunningham-Rundles C, Etzioni A, Holland SM, Klein C, Nonoyama S, Ochs HD, Oksenhendler E, Puck JM, Sullivan KE, Tang ML, Franco JL, Gaspar HB TITLE Primary Immunodeficiency Diseases: an Update on the Classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency 2015. JOURNAL J Clin Immunol 35:696-726 (2015) DOI:10.1007/s10875-015-0201-1 PMID:17952897 (RAG1, RAG2, DCLRE1C, ADA) AUTHORS Geha RS, Notarangelo LD, Casanova JL, Chapel H, Conley ME, Fischer A, Hammarstrom L, Nonoyama S, Ochs HD, Puck JM, Roifman C, Seger R, Wedgwood J. TITLE Primary immunodeficiency diseases: an update from the International Union of Immunological Societies Primary Immunodeficiency Diseases Classification Committee. JOURNAL J Allergy Clin Immunol 120:776-94 (2007) DOI:10.1016/j.jaci.2007.08.053 PMID:19043417 (AK2) AUTHORS Pannicke U, Honig M, Hess I, Friesen C, Holzmann K, Rump EM, Barth TF, Rojewski MT, Schulz A, Boehm T, Friedrich W, Schwarz K TITLE Reticular dysgenesis (aleukocytosis) is caused by mutations in the gene encoding mitochondrial adenylate kinase 2. JOURNAL Nat Genet 41:101-5 (2009) DOI:10.1038/ng.265 PMID:19075392 (PRKDC) AUTHORS van der Burg M, Ijspeert H, Verkaik NS, Turul T, Wiegant WW, Morotomi-Yano K, Mari PO, Tezcan I, Chen DJ, Zdzienicka MZ, van Dongen JJ, van Gent DC TITLE A DNA-PKcs mutation in a radiosensitive T-B- SCID patient inhibits Artemis activation and nonhomologous end-joining. JOURNAL J Clin Invest 119:91-8 (2009) DOI:10.1172/JCI37141 |