| H00100 | |
| H number | H00100 |
| Name | Neutropenic disorders |
| Description | Neutropenias represents a series of potentially life-threatening disorders characterised by a reduction in circulating neutrophils. Since neutrophils play a major role in host defense against bacteria, neutropenia patients suffer from frequent episodes of opportunistic bacterial infections. Severe congenital neutropenia (SCN) is a rare neutropenia with a bone marrow maturation arrest of granulocytic differentiation. Kostmann syndrome is an autosomal recessive SCN. The characteristic maturation arrest and the lack of mature neutrophils in peripheral blood of patients with Kostmann syndrome can be explained by the deletion of an anti-apoptotic factor (HAX-1) in myeloid cells of these patients. Heterozygous mutations in the protooncogene growth factor-independent 1 (GFI1) gene are also associated with SCN. In patients with autosomal dominant cyclic neutropenia (CyN), a condition with oscillating neutrophil counts but less severe clinical symptoms, heterozygous mutations in ELA-2/ELANE were discovered. Patients with X-linked severe congenital neutropenia (SCN) have been reported with activating mutations in Wiskott-Aldrich syndrome protein (WASp) leading to a constitutively-active form of the protein, and unregulated actin polymerization. |
| Category | Primary immunodeficiency |
| Network | - |
| Gene | (SCN1) ELANE [HSA:1991] [KO:K01327] (SCN2/NI-CINA) GFI1 [HSA:2672] [KO:K09223] (SCN3) HAX1 [HSA:10456] [KO:K16220] (SCN4) G6PC3 [HSA:92579] [KO:K01084] (SCN5) VPS45 [HSA:11311] [KO:K12479] (SCN6) JAGN1 [HSA:84522] [KO:K25789] (SCN7) CSF3R [HSA:1441] [KO:K05061] (SCN8) SRP54 [HSA:6729] [KO:K03106] (SCN9) CLPB [HSA:81570] [KO:K03695] (SCNX) WAS [HSA:7454] [KO:K05747] |
| Pathogen | - |
| Env factor | - |
| Carcinogen | - |
| Drug | Filgrastim [DR:D03235] Pegfilgrastim [DR:D06889] |
| Comment | - |
| Other DBs | ICD-11: 4B00.0 ICD-10: D70 OMIM: 202700 613107 607847 610738 612541 615285 616022 617014 618752 619813 300299 |
| Reference | PMID:17162365 (SCN1, SCN2, SCNX) AUTHORS Kumar A, Teuber SS, Gershwin ME. TITLE Current perspectives on primary immunodeficiency diseases. JOURNAL Clin Dev Immunol 13:223-59 (2006) DOI:10.1080/17402520600800705 PMID:18424339 (SCN1, SCN2, SCN3, SCN7) 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:19811314 (SCN1, SCN2, SCN3, SCN4, SCN7) AUTHORS Rezaei N, Moazzami K, Aghamohammadi A, Klein C TITLE Neutropenia and primary immunodeficiency diseases. JOURNAL Int Rev Immunol 28:335-66 (2009) DOI:10.1080/08830180902995645 PMID:19118303 (SCN4) AUTHORS Boztug K, Appaswamy G, Ashikov A, Schaffer AA, Salzer U, Diestelhorst J, Germeshausen M, Brandes G, Lee-Gossler J, Noyan F, Gatzke AK, Minkov M, Greil J, Kratz C, Petropoulou T, Pellier I, Bellanne-Chantelot C, Rezaei N, Monkemoller K, Irani-Hakimeh N, Bakker H, Gerardy-Schahn R, Zeidler C, Grimbacher B, Welte K, Klein C TITLE A syndrome with congenital neutropenia and mutations in G6PC3. JOURNAL N Engl J Med 360:32-43 (2009) DOI:10.1056/NEJMoa0805051 PMID:23738510 (SCN5) AUTHORS Vilboux T, Lev A, Malicdan MC, Simon AJ, Jarvinen P, Racek T, Puchalka J, Sood R, Carrington B, Bishop K, Mullikin J, Huizing M, Garty BZ, Eyal E, Wolach B, Gavrieli R, Toren A, Soudack M, Atawneh OM, Babushkin T, Schiby G, Cullinane A, Avivi C, Polak-Charcon S, Barshack I, Amariglio N, Rechavi G, van der Werff ten Bosch J, Anikster Y, Klein C, Gahl WA, Somech R TITLE A congenital neutrophil defect syndrome associated with mutations in VPS45. JOURNAL N Engl J Med 369:54-65 (2013) DOI:10.1056/NEJMoa1301296 PMID:25129144 (SCN6) AUTHORS Boztug K, Jarvinen PM, Salzer E, Racek T, Monch S, Garncarz W, Gertz EM, Schaffer AA, Antonopoulos A, Haslam SM, Schieck L, Puchalka J, Diestelhorst J, Appaswamy G, Lescoeur B, Giambruno R, Bigenzahn JW, Elling U, Pfeifer D, Conde CD, Albert MH, Welte K, Brandes G, Sherkat R, van der Werff Ten Bosch J, Rezaei N, Etzioni A, Bellanne-Chantelot C, Superti-Furga G, Penninger JM, Bennett KL, von Blume J, Dell A, Donadieu J, Klein C TITLE JAGN1 deficiency causes aberrant myeloid cell homeostasis and congenital neutropenia. JOURNAL Nat Genet 46:1021-7 (2014) DOI:10.1038/ng.3069 PMID:24753537 (SCN7) AUTHORS Triot A, Jarvinen PM, Arostegui JI, Murugan D, Kohistani N, Dapena Diaz JL, Racek T, Puchalka J, Gertz EM, Schaffer AA, Kotlarz D, Pfeifer D, Diaz de Heredia Rubio C, Ozdemir MA, Patiroglu T, Karakukcu M, Sanchez de Toledo Codina J, Yague J, Touw IP, Unal E, Klein C TITLE Inherited biallelic CSF3R mutations in severe congenital neutropenia. JOURNAL Blood 123:3811-7 (2014) DOI:10.1182/blood-2013-11-535419 PMID:28972538 (SCN8) AUTHORS Carapito R, Konantz M, Paillard C, Miao Z, Pichot A, Leduc MS, Yang Y, Bergstrom KL, Mahoney DH, Shardy DL, Alsaleh G, Naegely L, Kolmer A, Paul N, Hanauer A, Rolli V, Muller JS, Alghisi E, Sauteur L, Macquin C, Morlon A, Sancho CS, Amati-Bonneau P, Procaccio V, Mosca-Boidron AL, Marle N, Osmani N, Lefebvre O, Goetz JG, Unal S, Akarsu NA, Radosavljevic M, Chenard MP, Rialland F, Grain A, Bene MC, Eveillard M, Vincent M, Guy J, Faivre L, Thauvin-Robinet C, Thevenon J, Myers K, Fleming MD, Shimamura A, Bottollier-Lemallaz E, Westhof E, Lengerke C, Isidor B, Bahram S TITLE Mutations in signal recognition particle SRP54 cause syndromic neutropenia with Shwachman-Diamond-like features. JOURNAL J Clin Invest 127:4090-4103 (2017) DOI:10.1172/JCI92876 PMID:34115842 (SCN9) AUTHORS Warren JT, Cupo RR, Wattanasirakul P, Spencer DH, Locke AE, Makaryan V, Bolyard AA, Kelley ML, Kingston NL, Shorter J, Bellanne-Chantelot C, Donadieu J, Dale DC, Link DC TITLE Heterozygous variants of CLPB are a cause of severe congenital neutropenia. JOURNAL Blood 139:779-791 (2022) DOI:10.1182/blood.2021010762 |