KEGG   DISEASE: H00107Help
Entry
H00107                      Disease                                

Name
Other well-defined immunodeficiency syndromes, including the following eight diseases:
Wiskott-Aldrich syndrome;
DiGeorge syndrome;
Hyper-IgE syndrome;
X-linked lymphoproliferative syndrome;
Lymphoproliferative syndrome, EBV-associated, autosomal, 1;
Immunodeficiency, Polyendocrinopathy, Enteropathy, X-linked Syndrome (IPEX);
Cartilage-Hair Hypoplasia;
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED)
Description
Wiskott-Aldrich syndrome (WAS) is an X-linked recessive disease and characterized by immune dysregulation and microthrombocytopenia. Several nonsense and missense mutations as well as deletions and insertions of the WAS gene have been identified in WAS patients. DiGeorge/velocardiofacial syndrome (DGS) is a congenital immune disorder characterized by lack of embryonic development or underdevelopment of the thymus and surrounding organs. The DGS is a member of a group of disorders that have in common a chromosome deletion involving 22q11.2 (the DiGeorge syndrome chromosome region, or DGCR). Hyper-IgE syndrome (HIES) is characterized by atopic dermatitis associated with extremely high serum IgE levels and susceptibility to infections with extracellular bacteria. Dominant-negative mutations in the signal transducer and activator of transcription 3 (STAT3) gene result in the classical multisystem form of HIES, whereas a null mutation in the tyrosine kinase 2 (TYK2) gene causes an autosomal recessive HIES associated with viral and mycobacterial infections. X-linked lymphoproliferative syndrome (XLP) is a rare primary immunodeficiency, with manifestations ranging from fatal infectious mononucleosis to B cell lymphomas and hypogammaglobulinemia. Mutations in the X-linked inhibitor of apoptosis (XIAP) as well as in a distinct gene, SLAM-associated protein (SAP/DSP1/SH2D1A) have been identified in patients with XLP. Recently, it has been shown that a homozygous mutation in the SH2 domain of the IL-2-inducible T-cell kinase (ITK) gene is associated with fatal Epstein Barr virus associated lymphoproliferation, with a clinical picture similar to that seen in XLP. Immune dysregulation, polyendocrinopathy, enteropathy and X-linked (IPEX) syndrome and autoimmune polyendocrinopathy, candidiasis, ectodermal dysplasia (APECED) are examples of dysregulated immunity resulting in a disturbed tolerance and multiple autoimmune phenomena. IPEX is caused by mutations in the FOXP3 gene, and APECED results from mutations in the autoimmune regulator (AIRE) gene. Cartilage hair hypoplasia (CHH) is due to either the homozygous or compound heterozygous mutations in the nuclear encoded, non-coding RNA gene RMRP.
Category
Primary immunodeficiency
BRITE hierarchy
Pathway
Primary immunodeficiency
Gene
WAS [HSA:7454] [KO:K05747]
TBX1 [HSA:6899] [KO:K10175]
STAT3 [HSA:6774] [KO:K04692]
TYK2 [HSA:7297] [KO:K11219]
SH2D1A [HSA:4068] [KO:K07990]
XIAP [HSA:331] [KO:K04725]
ITK [HSA:3702] [KO:K07363]
AIRE [HSA:326] [KO:K10603]
FOXP3 [HSA:50943] [KO:K10163]
RMRP [HSA:6023]
Other DBs
Reference
PMID:17162365 (gene)
  Authors
Kumar A, Teuber SS, Gershwin ME.
  Title
Current perspectives on primary immunodeficiency diseases.
  Journal
Clin Dev Immunol 13:223-59 (2006)
Reference
PMID:9737224 (gene)
  Authors
Ten RM.
  Title
Primary immunodeficiencies.
  Journal
Mayo Clin Proc 73:865-72 (1998)
Reference
PMID:15096561 (description, gene)
  Authors
Lim MS, Elenitoba-Johnson KS.
  Title
The molecular pathology of primary immunodeficiencies.
  Journal
J Mol Diagn 6:59-83 (2004)
Reference
PMID:19425169 (gene)
  Authors
Huck K, Feyen O, Niehues T, Ruschendorf F, Hubner N, Laws HJ, Telieps T, Knapp S, Wacker HH, Meindl A, Jumaa H, Borkhardt A
  Title
Girls homozygous for an IL-2-inducible T cell kinase mutation that leads to protein deficiency develop fatal EBV-associated lymphoproliferation.
  Journal
J Clin Invest 119:1350-8 (2009)
Reference
PMID:21109689 (description, gene)
  Authors
Stepensky P, Weintraub M, Yanir A, Revel-Vilk S, Krux F, Huck K, Linka RM, Shaag A, Elpeleg O, Borkhardt A, Resnick IB
  Title
IL-2-inducible T-cell kinase deficiency: clinical presentation and therapeutic approach.
  Journal
Haematologica 96:472-6 (2011)
Reference
PMID:18264745 (description, gene)
  Authors
Moraes-Vasconcelos D, Costa-Carvalho BT, Torgerson TR, Ochs HD
  Title
Primary immune deficiency disorders presenting as autoimmune diseases: IPEX and APECED.
  Journal
J Clin Immunol 28 Suppl 1:S11-9 (2008)
Reference
PMID:19717292 (description, gene)
  Authors
Minegishi Y
  Title
Hyper-IgE syndrome.
  Journal
Curr Opin Immunol 21:487-92 (2009)
Reference
PMID:16838329 (description, gene)
  Authors
Hermanns P, Tran A, Munivez E, Carter S, Zabel B, Lee B, Leroy JG
  Title
RMRP mutations in cartilage-hair hypoplasia.
  Journal
Am J Med Genet A 140:2121-30 (2006)
Reference
PMID:19595300 (description, gene)
  Authors
Rumble JM, Oetjen KA, Stein PL, Schwartzberg PL, Moore BB, Duckett CS
  Title
Phenotypic differences between mice deficient in XIAP and SAP, two factors targeted in X-linked lymphoproliferative syndrome (XLP).
  Journal
Cell Immunol 259:82-9 (2009)
Reference
PMID:18424339 (gene)
  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)
Reference
PMID:17952897 (gene)
  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)

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