| H00085 | |
| H number | H00085 |
| Name | Agammaglobulinemias |
| Description | There are three major categories of antibody deficiencies: (a) defects in early B cell development, (b) hyper-IgM syndromes (also called class switch recombination defects), and (c) common variable immunodeficiency (CVID). Category (a) consists of agammaglobulinaemias (AGM). Defects in early B cell development are characterized by the onset of recurrent bacterial infections in the first 5 years of life, profound hypogammaglobulinemia, markedly reduced or absent B cells in the peripheral circulation, and (in the bone marrow) a severe block in B cell differentiation before the production of surface immunoglobulin-positive B cells. Mutations in Btk, the gene responsible for X-linked agammaglobulinemia (XLA), account for approximately 85% of affected patients. Approximately half of the remaining patients have mutations in genes encoding components of the pre-B cell receptor (pre-BCR) or BCR, including mu heavy chain (IGHM); the signal transduction molecules Ig-alpha (CD79A) and Ig-beta (CD79B); and lambda 5 (IGLL1), which forms the surrogate light chain with Vpre-B. A small number of patients with defects in BLNK, a scaffold protein that assembles signal transduction molecules activated by cross-linking of the BCR, have been reported. |
| Category | Immune system disease |
| Network | nt06528(H00085) Calcium signaling |
| Gene | (AGMX1) BTK [HSA:695] [KO:K07370] (AGMX2) SH3KBP1 [HSA:30011] [KO:K12470] (AGM2) IGLL1 [HSA:3543] [KO:K06554] (AGM3) CD79A [HSA:973] [KO:K06506] (AGM4) BLNK [HSA:29760] [KO:K07371] (AGM5) LRRC8A [HSA:56262] [KO:K22038] (AGM6) CD79B [HSA:974] [KO:K06507] (AGM7) PIK3R1 [HSA:5295] [KO:K02649] (AGM8) TCF3 [HSA:6929] [KO:K09063] (AGM9) SLC39A7 [HSA:7922] [KO:K14713] (AGM10) SPI1 [HSA:6688] [KO:K09438] |
| Pathogen | - |
| Env factor | - |
| Carcinogen | - |
| Drug | - |
| Comment | AGM1 is caused by homozygous or compound heterozygous mutation in the mu heavy-chain gene (IGHM). |
| Other DBs | ICD-11: 4A01.00 ICD-10: D80 MeSH: D000361 OMIM: 300755 300310 601495 613500 613501 613502 613506 612692 615214 616941 619693 619707 |
| Reference | PMID:19302039 AUTHORS Conley ME, Dobbs AK, Farmer DM, Kilic S, Paris K, Grigoriadou S, Coustan-Smith E, Howard V, Campana D TITLE Primary B cell immunodeficiencies: comparisons and contrasts. JOURNAL Annu Rev Immunol 27:199-227 (2009) DOI:10.1146/annurev.immunol.021908.132649 PMID:18424339 AUTHORS Morra M, Geigenmuller U, Curran J, Rainville IR, Brennan T, Curtis J, Reichert V, Hovhannisyan H, Majzoub J, Miller DT. TITLE Genetic diagnosis of primary immune deficiencies. JOURNAL Immunol Allergy Clin North Am 28:387-412, x (2008) DOI:10.1016/j.iac.2008.01.004 PMID:32552675 (AGMX1) AUTHORS Gao S, Hu S, Duan H, Wang L, Kong X TITLE Clinical characteristics and prenatal diagnosis for 22 families in Henan Province of China with X-linked agammaglobulinemia (XLA) related to Bruton's tyrosine kinase (BTK) gene mutations. JOURNAL BMC Med Genet 21:131 (2020) DOI:10.1186/s12881-020-01063-5 PMID:29636373 (AGMX2) AUTHORS Keller B, Shoukier M, Schulz K, Bhatt A, Heine I, Strohmeier V, Speckmann C, Engels N, Warnatz K, Wienands J TITLE Germline deletion of CIN85 in humans with X chromosome-linked antibody deficiency. JOURNAL J Exp Med 215:1327-1336 (2018) DOI:10.1084/jem.20170534 PMID:8890099 (AGM1) AUTHORS Yel L, Minegishi Y, Coustan-Smith E, Buckley RH, Trubel H, Pachman LM, Kitchingman GR, Campana D, Rohrer J, Conley ME TITLE Mutations in the mu heavy-chain gene in patients with agammaglobulinemia. JOURNAL N Engl J Med 335:1486-93 (1996) DOI:10.1056/NEJM199611143352003 PMID:9419212 (AGM2) AUTHORS Minegishi Y, Coustan-Smith E, Wang YH, Cooper MD, Campana D, Conley ME TITLE Mutations in the human lambda5/14.1 gene result in B cell deficiency and agammaglobulinemia. JOURNAL J Exp Med 187:71-7 (1998) DOI:10.1084/jem.187.1.71 PMID:10525050 (AGM3) AUTHORS Minegishi Y, Coustan-Smith E, Rapalus L, Ersoy F, Campana D, Conley ME TITLE Mutations in Igalpha (CD79a) result in a complete block in B-cell development. JOURNAL J Clin Invest 104:1115-21 (1999) DOI:10.1172/JCI7696 PMID:24582315 (AGM4) AUTHORS Lagresle-Peyrou C, Millili M, Luce S, Boned A, Sadek H, Rouiller J, Frange P, Cros G, Cavazzana M, Andre-Schmutz I, Schiff C TITLE The BLNK adaptor protein has a nonredundant role in human B-cell differentiation. JOURNAL J Allergy Clin Immunol 134:145-54 (2014) DOI:10.1016/j.jaci.2013.12.1083 PMID:14660746 (AGM5) AUTHORS Sawada A, Takihara Y, Kim JY, Matsuda-Hashii Y, Tokimasa S, Fujisaki H, Kubota K, Endo H, Onodera T, Ohta H, Ozono K, Hara J TITLE A congenital mutation of the novel gene LRRC8 causes agammaglobulinemia in humans. JOURNAL J Clin Invest 112:1707-13 (2003) DOI:10.1172/JCI18937 PMID:17675462 (AGM6) AUTHORS Dobbs AK, Yang T, Farmer D, Kager L, Parolini O, Conley ME TITLE Cutting edge: a hypomorphic mutation in Igbeta (CD79b) in a patient with immunodeficiency and a leaky defect in B cell development. JOURNAL J Immunol 179:2055-9 (2007) DOI:10.4049/jimmunol.179.4.2055 PMID:22351933 (AGM7) AUTHORS Conley ME, Dobbs AK, Quintana AM, Bosompem A, Wang YD, Coustan-Smith E, Smith AM, Perez EE, Murray PJ TITLE Agammaglobulinemia and absent B lineage cells in a patient lacking the p85alpha subunit of PI3K. JOURNAL J Exp Med 209:463-70 (2012) DOI:10.1084/jem.20112533 PMID:24216514 (AGM8) AUTHORS Boisson B, Wang YD, Bosompem A, Ma CS, Lim A, Kochetkov T, Tangye SG, Casanova JL, Conley ME TITLE A recurrent dominant negative E47 mutation causes agammaglobulinemia and BCR(-) B cells. JOURNAL J Clin Invest 123:4781-5 (2013) DOI:10.1172/JCI71927 PMID:30718914 (AGM9) AUTHORS Anzilotti C, Swan DJ, Boisson B, Deobagkar-Lele M, Oliveira C, Chabosseau P, Engelhardt KR, Xu X, Chen R, Alvarez L, Berlinguer-Palmini R, Bull KR, Cawthorne E, Cribbs AP, Crockford TL, Dang TS, Fearn A, Fenech EJ, de Jong SJ, Lagerholm BC, Ma CS, Sims D, van den Berg B, Xu Y, Cant AJ, Kleiner G, Leahy TR, de la Morena MT, Puck JM, Shapiro RS, van der Burg M, Chapman JR, Christianson JC, Davies B, McGrath JA, Przyborski S, Santibanez Koref M, Tangye SG, Werner A, Rutter GA, Padilla-Parra S, Casanova JL, Cornall RJ, Conley ME, Hambleton S TITLE An essential role for the Zn(2+) transporter ZIP7 in B cell development. JOURNAL Nat Immunol 20:350-361 (2019) DOI:10.1038/s41590-018-0295-8 PMID:33951726 (AGM10) AUTHORS Le Coz C, Nguyen DN, Su C, Nolan BE, Albrecht AV, Xhani S, Sun D, Demaree B, Pillarisetti P, Khanna C, Wright F, Chen PA, Yoon S, Stiegler AL, Maurer K, Garifallou JP, Rymaszewski A, Kroft SH, Olson TS, Seif AE, Wertheim G, Grant SFA, Vo LT, Puck JM, Sullivan KE, Routes JM, Zakharova V, Shcherbina A, Mukhina A, Rudy NL, Hurst ACE, Atkinson TP, Boggon TJ, Hakonarson H, Abate AR, Hajjar J, Nicholas SK, Lupski JR, Verbsky J, Chinn IK, Gonzalez MV, Wells AD, Marson A, Poon GMK, Romberg N TITLE Constrained chromatin accessibility in PU.1-mutated agammaglobulinemia patients. JOURNAL J Exp Med 218:e20201750 (2021) DOI:10.1084/jem.20201750 |