KEGG DISEASE: T-B+Severe combined immunodeficiency

DISEASE: T-B+Severe combined immunodeficiency

Entry

H00091                      Disease

Name

T-B+Severe combined immunodeficiency

Supergrp

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

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. SCIDs with lack of circulating T cells but a normal number of B cells accounts for 30 to 50% of all cases of human SCIDs. The most frequent form of SCID, X-linked SCID (SCID-X1), is caused by mutations in the gamma-chain-encoding gene. Gamma-chain is a common subunit shared by several cytokine receptors. It results in an absence of both mature T lymphocytes and NK lymphocytes. The second most common variant is autosomal recessive and due to mutations of the JAK3 gene. IL-7R alpha gene mutations result in a pure T-cell deficiency. Rare cases of SCID consisting of pure T-cell deficiencies have been attributed to defects in key proteins involved in pre-TCR/TCR signaling. Deficiency in the CD45 phosphatase has been reported in two cases of SCID, while defects in CD3 delta, CD3 epsilon and CD3 zeta have also been described.

Category

Primary immunodeficiency

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
    H00091  T-B+Severe combined immunodeficiency
Pathway-based classification of diseases [BR:br08402]
Replication and repair
  nt06504  Base excision repair
   H00091  T-B+Severe combined immunodeficiency
  nt06502  Nucleotide excision repair
   H00091  T-B+Severe combined immunodeficiency
  nt06506  Double-strand break repair
   H00091  T-B+Severe combined immunodeficiency
Signal transduction
  nt06518  JAK-STAT signaling
   H00091  T-B+Severe combined immunodeficiency
Immune system
  nt06537  TCR/BCR signaling
   H00091  T-B+Severe combined immunodeficiency

Pathway

hsa04630

JAK-STAT signaling pathway

hsa04660

T cell receptor signaling pathway

Network

nt06502 Nucleotide excision repair
nt06504 Base excision repair
nt06506 Double-strand break repair
nt06518 JAK-STAT signaling
nt06537 TCR/BCR signaling

Gene

JAK3 [HSA:3718] [KO:K11218]
(SCIDX1) IL2RG [HSA:3561] [KO:K05070]
(IMD8) CORO1A [HSA:11151] [KO:K13882]
(IMD18) CD3E [HSA:916] [KO:K06451]
(IMD19) CD3D [HSA:915] [KO:K06450]
(IMD25) CD247 [HSA:919] [KO:K06453]
(IMD49) BCL11B [HSA:64919] [KO:K22046]
(IMD104) IL7R [HSA:3575] [KO:K05072]
(IMD105) PTPRC [HSA:5788] [KO:K06478]
(IMD122) POLD3 [HSA:10714] [KO:K03504]

Other DBs

ICD-11:

4A01.10

ICD-10:

D81

MeSH:

D053632

OMIM:

600802 300400 615401 615615 615617 610163 617237 608971 619924 620869

Reference

PMID:15661024

Authors

Fischer A, Le Deist F, Hacein-Bey-Abina S, Andre-Schmutz I, Basile Gde S, de Villartay JP, Cavazzana-Calvo M.

Title

Severe combined immunodeficiency. A model disease for molecular immunology and therapy.

Journal

Immunol Rev 203:98-109 (2005)
DOI:10.1111/j.0105-2896.2005.00223.x

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:17952897

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

Reference

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

Reference

PMID:7659163 (JAK3)

Authors

Macchi P, Villa A, Giliani S, Sacco MG, Frattini A, Porta F, Ugazio AG, Johnston JA, Candotti F, O'Shea JJ, et al.

Title

Mutations of Jak-3 gene in patients with autosomal severe combined immune deficiency (SCID).

Journal

Nature 377:65-8 (1995)
DOI:10.1038/377065a0

Reference

PMID:8462096 (SCIDX1)

Authors

Noguchi M, Yi H, Rosenblatt HM, Filipovich AH, Adelstein S, Modi WS, McBride OW, Leonard WJ

Title

Interleukin-2 receptor gamma chain mutation results in X-linked severe combined immunodeficiency in humans.

Journal

Cell 73:147-57 (1993)
DOI:10.1016/0092-8674(93)90167-o

Reference

PMID:19097825 (IMD8)

Authors

Shiow LR, Paris K, Akana MC, Cyster JG, Sorensen RU, Puck JM

Title

Severe combined immunodeficiency (SCID) and attention deficit hyperactivity disorder (ADHD) associated with a Coronin-1A mutation and a chromosome 16p11.2 deletion.

Journal

Clin Immunol 131:24-30 (2009)
DOI:10.1016/j.clim.2008.11.002

Reference

PMID:15546002 (IMD18 IMD19)

Authors

de Saint Basile G, Geissmann F, Flori E, Uring-Lambert B, Soudais C, Cavazzana-Calvo M, Durandy A, Jabado N, Fischer A, Le Deist F

Title

Severe combined immunodeficiency caused by deficiency in either the delta or the epsilon subunit of CD3.

Journal

J Clin Invest 114:1512-7 (2004)
DOI:10.1172/JCI22588

Reference

PMID:16672702 (IMD25)

Authors

Rieux-Laucat F, Hivroz C, Lim A, Mateo V, Pellier I, Selz F, Fischer A, Le Deist F

Title

Inherited and somatic CD3zeta mutations in a patient with T-cell deficiency.

Journal

N Engl J Med 354:1913-21 (2006)
DOI:10.1056/NEJMoa053750

Reference

PMID:27959755 (IMD49)

Authors

Punwani D, Zhang Y, Yu J, Cowan MJ, Rana S, Kwan A, Adhikari AN, Lizama CO, Mendelsohn BA, Fahl SP, Chellappan A, Srinivasan R, Brenner SE, Wiest DL, Puck JM

Title

Multisystem Anomalies in Severe Combined Immunodeficiency with Mutant BCL11B.

Journal

N Engl J Med 375:2165-2176 (2016)
DOI:10.1056/NEJMoa1509164

Reference

PMID:9843216 (IMD104)

Authors

Puel A, Ziegler SF, Buckley RH, Leonard WJ

Title

Defective IL7R expression in T(-)B(+)NK(+) severe combined immunodeficiency.

Journal

Nat Genet 20:394-7 (1998)
DOI:10.1038/3877

Reference

PMID:10700239 (IMD105)

Authors

Kung C, Pingel JT, Heikinheimo M, Klemola T, Varkila K, Yoo LI, Vuopala K, Poyhonen M, Uhari M, Rogers M, Speck SH, Chatila T, Thomas ML

Title

Mutations in the tyrosine phosphatase CD45 gene in a child with severe combined immunodeficiency disease.

Journal

Nat Med 6:343-5 (2000)
DOI:10.1038/73208

Reference

PMID:37030525 (IMD122)

Authors

Mehawej C, Chouery E, Azar-Atallah S, Shebaby W, Delague V, Mansour I, Mustapha M, Lefranc G, Megarbane A

Title

POLD3 deficiency is associated with severe combined immunodeficiency, neurodevelopmental delay, and hearing impairment.

Journal

Clin Immunol 251:109326 (2023)
DOI:10.1016/j.clim.2023.109326

» Japanese version

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Network (13)   
   KEGG NETWORK (5)   
   KEGG VARIANT (8)   
Disease (10)   
   OMIM (10)   
Gene (20)   
   KEGG ORTHOLOGY (10)   
   KEGG GENES (10)   
Literature (13)   
   PubMed (13)   
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