KEGG DISEASE: Agammaglobulinemias

DISEASE: Agammaglobulinemias

Entry

H00085                      Disease

Name

Agammaglobulinemias

Subgroup

Agammaglobulinaemia, X-linked (AGMX)

Supergrp

Disorders of adaptive immunity [DS:H02526]
Primary immunodeficiency disease [DS:H01725]

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

Brite

Human diseases in ICD-11 classification [BR:br08403]
04 Diseases of the immune system
  Primary immunodeficiencies
   4A01  Primary immunodeficiencies due to disorders of adaptive immunity
    H00085  Agammaglobulinemias
Pathway-based classification of diseases [BR:br08402]
Immune system
  nt06537  TCR/BCR signaling
   H00085  Agammaglobulinemias

Pathway

hsa04151 PI3K-Akt signaling pathway

hsa04662 B cell receptor signaling pathway

Network

nt06537 TCR/BCR 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]
(AGM8A/8B) TCF3 [HSA:6929] [KO:K09063]
(AGM9) SLC39A7 [HSA:7922] [KO:K14713]
(AGM10) SPI1 [HSA:6688] [KO:K09438]

Comment

AGM1 is caused by homozygous or compound heterozygous mutation in the mu heavy-chain gene (IGHM).

Other DBs

ICD-11:

4A01.00

MeSH:

D000361

OMIM:

300755 300310 601495 613500 613501 613502 613506 612692 615214 616941 619824 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

Reference

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

Reference

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

Reference

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

Reference

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

Reference

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

Reference

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

Reference

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

Reference

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

Reference

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

Reference

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

Reference

PMID:24216514 (AGM8A)

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

Reference

PMID:28532655 (AGM8B)

Authors

Ben-Ali M, Yang J, Chan KW, Ben-Mustapha I, Mekki N, Benabdesselem C, Mellouli F, Bejaoui M, Yang W, Aissaoui L, Lau YL, Barbouche MR

Title

Homozygous transcription factor 3 gene (TCF3) mutation is associated with severe hypogammaglobulinemia and B-cell acute lymphoblastic leukemia.

Journal

J Allergy Clin Immunol 140:1191-1194.e4 (2017)
DOI:10.1016/j.jaci.2017.04.037

Reference

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

Reference

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

LinkDB

» Japanese version

DISEASE: Growth hormone deficiency

Entry

H00254                      Disease

Name

Growth hormone deficiency;
Pituitary dwarfism

Subgroup

Isolated growth hormone deficiency (IGHD) [DS:H02035]
Combined pituitary hormone deficiency (CPHD) [DS:H02036]
Laron syndrome (PD2) [DS:H02037]
X-linked panhypopituitarism (PHPX) [DS:H02038]
Kowarski syndrome [DS:H02039]
Growth hormone deficiency, isolated partial (GHDP)

Supergrp

Hypopituitarism [DS:H01700]

Description

Growth hormone deficiency, formerly known as Pituitary dwarfism, is a heterogeneous condition characterized by growth retardation with short stature and normal body proportions caused by growth hormone deficiency.

Category

Endocrine and metabolic disease

Brite

Human diseases in ICD-11 classification [BR:br08403]
05 Endocrine, nutritional or metabolic diseases
  Endocrine diseases
   Disorders of the pituitary hormone system
    5A61  Hypofunction or certain other specified disorders of pituitary gland
     H00254  Growth hormone deficiency
Pathway-based classification of diseases [BR:br08402]
Immune system
  nt06537  TCR/BCR signaling
   H00254  Growth hormone deficiency
Endocrine system
  nt06324  GHRH-GH-IGF signaling
   H00254  Growth hormone deficiency

Pathway

hsa04662

B cell receptor signaling pathway

hsa04935

Growth hormone synthesis, secretion and action

hsa04080

Neuroactive ligand-receptor interaction

Network

nt06324 GHRH-GH-IGF signaling
nt06537 TCR/BCR signaling

Gene

(IGHD1A/1B/2) GH1 [HSA:2688] [KO:K05438]
(IGHD3) BTK [HSA:695] [KO:K07370]
(IGHD4) GHRHR [HSA:2692] [KO:K04584]
(CPHD1) POU1F1 [HSA:5449] [KO:K09363]
(CPHD2) PROP1 [HSA:5626] [KO:K09327]
(CPHD3) LHX3 [HSA:8022] [KO:K09374]
(CPHD4) LHX4 [HSA:89884] [KO:K09374]
(CPHD5) HESX1 [HSA:8820] [KO:K09354]
(CPHD6) OTX2 [HSA:5015] [KO:K18490]
(CPHD7/IGHD5) RNPC3 [HSA:55599] [KO:K13157]
(CPHD8) ROBO1 [HSA:6091] [KO:K06753]
(PD2) GHR [HSA:2690] [KO:K05080]
(PHPX) SOX3 [HSA:6658] [KO:K09267]
(GHDP) GHSR [HSA:2693] [KO:K04284]

Drug

Somatropin [DR:D02691]
Somapacitan [DR:D11194]
Somatrogon [DR:D10990]
Lonapegsomatropin [DR:D11486]

Other DBs

ICD-11:

5A61.0 5A61.3

MeSH:

D004393

OMIM:

615925

Reference

PMID:7868072

Authors

Perez Jurado LA, Argente J

Title

Molecular basis of familial growth hormone deficiency.

Journal

Horm Res 42:189-97 (1994)
DOI:10.1159/000184192

Reference

PMID:9799079

Authors

Procter AM, Phillips JA 3rd, Cooper DN

Title

The molecular genetics of growth hormone deficiency.

Journal

Hum Genet 103:255-72 (1998)
DOI:10.1007/s004390050815

Reference

PMID:12201208

Authors

Hayashi Y, Kamijo T, Ogawa M, Seo H

Title

Familial isolated growth hormone deficiency: genetics and pathophysiology.

Journal

Endocr J 49:265-72 (2002)
DOI:10.1507/endocrj.49.265

Reference

PMID:17965963

Authors

Hernandez LM, Lee PD, Camacho-Hubner C

Title

Isolated growth hormone deficiency.

Journal

Pituitary 10:351-7 (2007)
DOI:10.1007/s11102-007-0073-3

Reference

PMID:17336732

Authors

Mullis PE

Title

Genetics of growth hormone deficiency.

Journal

Endocrinol Metab Clin North Am 36:17-36 (2007)
DOI:10.1016/j.ecl.2006.11.010

Reference

PMID:8488849 (GHR)

Authors

Berg MA, Argente J, Chernausek S, Gracia R, Guevara-Aguirre J, Hopp M, Perez-Jurado L, Rosenbloom A, Toledo SP, Francke U

Title

Diverse growth hormone receptor gene mutations in Laron syndrome.

Journal

Am J Hum Genet 52:998-1005 (1993)

Reference

PMID:12428212 (SOX3)

Authors

Laumonnier F, Ronce N, Hamel BC, Thomas P, Lespinasse J, Raynaud M, Paringaux C, Van Bokhoven H, Kalscheuer V, Fryns JP, Chelly J, Moraine C, Briault S

Title

Transcription factor SOX3 is involved in X-linked mental retardation with growth hormone deficiency.

Journal

Am J Hum Genet 71:1450-5 (2002)
DOI:10.1086/344661

Reference

PMID:16511605 (GHSR)

Authors

Pantel J, Legendre M, Cabrol S, Hilal L, Hajaji Y, Morisset S, Nivot S, Vie-Luton MP, Grouselle D, de Kerdanet M, Kadiri A, Epelbaum J, Le Bouc Y, Amselem S

Title

Loss of constitutive activity of the growth hormone secretagogue receptor in familial short stature.

Journal

J Clin Invest 116:760-8 (2006)
DOI:10.1172/JCI25303

LinkDB

» Japanese version

DBGET integrated database retrieval system