| H00091 | |
| H number | H00091 |
| 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. 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 |
| Network | nt06518(H00091) JAK-STAT signaling nt06528(H00091) Calcium signaling |
| Gene | IL2RG [HSA:3561] [KO:K05070] JAK3 [HSA:3718] [KO:K11218] IL7R [HSA:3575] [KO:K05072] PTPRC [HSA:5788] [KO:K06478] CD3D [HSA:915] [KO:K06450] CD3E [HSA:916] [KO:K06451] CD247 [HSA:919] [KO:K06453] CORO1A [HSA:11151] [KO:K13882] BCL11B [HSA:64919] [KO:K22046] |
| Pathogen | - |
| Env factor | - |
| Carcinogen | - |
| Drug | - |
| Comment | - |
| Other DBs | ICD-11: 4A01.10 ICD-10: D81 MeSH: D053632 OMIM: 608971 300400 606367 610163 615401 617237 |
| 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 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: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 PMID:26482257 (IL2RG, JAK3, IL7R, PTPRC, CD3D, CD3E, CD247, CORO1A) 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:27959755 (BCL11B) 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 |