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MIFTS: 59

Severe Congenital Neutropenia

Categories: Blood diseases, Bone diseases, Cancer diseases, Endocrine diseases, Genetic diseases, Immune diseases, Neuronal diseases, Rare diseases
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Aliases & Classifications for Severe Congenital Neutropenia

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MalaCards integrated aliases for Severe Congenital Neutropenia:

Name: Severe Congenital Neutropenia 12 52 25 58 29 6 15 37 71
Congenital Neutropenia 25 29 6
Severe Infantile Genetic Neutropenia 25
Infantile Genetic Agranulocytosis 25
Neutropenia, Severe Congenital 54
Congenital Agranulocytosis 25
Kostmann's Agranulocytosis 25
Kostmann's Syndrome 25
Kostmann Disease 25

Characteristics:

Orphanet epidemiological data:

58
severe congenital neutropenia
Inheritance: Autosomal dominant,Autosomal recessive,X-linked recessive; Prevalence: 1-9/1000000 (Europe); Age of onset: Childhood; Age of death: any age;

Classifications:

MalaCards categories:
Global: Rare diseases Cancer diseases Genetic diseases
Anatomical: Blood diseases Bone diseases Immune diseases Neuronal diseases Endocrine diseases
See all MalaCards categories (disease lists)
ICD10: 32 33
Orphanet: 58  
Rare immunological diseases


External Ids:

Disease Ontology 12 DOID:0050590
ICD10 32 D70
MESH via Orphanet 44 C537592
ICD10 via Orphanet 33 D70
UMLS via Orphanet 72 C1853118
Orphanet 58 ORPHA42738
UMLS 71 C1853118
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Summaries for Severe Congenital Neutropenia

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NIH Rare Diseases : 52 The following summary is from Orphanet , a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 42738 Definition Severe congenital neutropenia is an immunodeficiency characterized by low levels of granulocytes (< 200/mm3) without an associated lymphocyte deficit. Epidemiology The prevalence in the general population is estimated at 1-1.7/333,300. Annual incidence is around 1/250,000 births. Clinical description This neutropenia leads to repeated bacterial or mycotic infections in various locations, mostly cutaneo-mucous, ear, nose, and throat, and pulmonary. Stomatological signs are almost always present after 2 years of age and are distinguished by erosive gingivitis, hemorrhage and pain, associated with papilla on the tongue and mucous membranes. Infections may be very severe or even lethal. Around 15% of patients evolve to acute leukemia or a myelodysplastic syndrome . Etiology To date, mutations in four genes have been implicated in severe congenital neutropenia. These include the neutrophil elastase gene (ELA2 ), the GFI1 gene, the HAX1 gene and activation genes of Wiskott Aldrich disease (WASP ). The combination of these mutations leads to a deficit in the production of neutrophils. Diagnostic methods The defining characteristic is cytology showing profound neutropenia associated with monocytosis. An isolated blockage at the promyelocyte stage of the myeloid series associated with eosinophilia and monocytosis is seen on myelogram. Differential diagnosis On the discovery of these features a complete biological assessment should be conducted to rule out several differential diagnoses, particularly lymphocytic immune deficiencies and autoimmune neutropenia. Antenatal diagnosis Prenatal diagnosis may be offered if the genotype is known. Genetic counseling The four mutations are transmitted differently: ELA2 and GFI1 are autosomal dominant , HAX1 is autosomal recessive , and WASP is X-linked recessive . Genetic counseling is essential and should take into account family history and the causal mutation. Management and treatment All febrile episodes or infections should be reviewed by a hospital and treated actively. Prophylactic antibiotics are used to prevent infections. If this is ineffective, hematopoietic growth factors (G-CSF in particular) can correct both neutropenia and the susceptibility to infections and can be administered either in response to infections or continuously. The dose of G-CSF required varies greatly. Continuous high dose G-CSF (more than 20?g/kg/day) encourages the onset of leukemia in the long term and therefore, in cases requiring continuous high dose treatment, bone marrow transplant should be considered. Prognosis The prognosis depends heavily on the quality of care and timeliness of treatment of severe infections, but also on the possibility of a bone marrow transplant, particularly in cases with malignant transformation . Visit the Orphanet disease page for more resources.

MalaCards based summary : Severe Congenital Neutropenia, also known as congenital neutropenia, is related to severe congenital neutropenia autosomal dominant and autosomal recessive severe congenital neutropenia. An important gene associated with Severe Congenital Neutropenia is CSF3R (Colony Stimulating Factor 3 Receptor), and among its related pathways/superpathways are Innate Immune System and Akt Signaling. The drugs Anti-Infective Agents and Antiviral Agents have been mentioned in the context of this disorder. Affiliated tissues include neutrophil, bone and myeloid, and related phenotypes are Decreased viability and Decreased viability

Disease Ontology : 12 A neutropenia characterized by a maturation arrest of granulopoiesis at the level or promyelocytes and early onset of severe bacterial infections.

Genetics Home Reference : 25 Severe congenital neutropenia is a condition that causes affected individuals to be prone to recurrent infections. People with this condition have a shortage (deficiency) of neutrophils, a type of white blood cell that plays a role in inflammation and in fighting infection. The deficiency of neutrophils, called neutropenia, is apparent at birth or soon afterward. It leads to recurrent infections beginning in infancy, including infections of the sinuses, lungs, and liver. Affected individuals can also develop fevers and inflammation of the gums (gingivitis) and skin. Approximately 40 percent of affected people have decreased bone density (osteopenia) and may develop osteoporosis, a condition that makes bones progressively more brittle and prone to fracture. In people with severe congenital neutropenia, these bone disorders can begin at any time from infancy through adulthood. Approximately 20 percent of people with severe congenital neutropenia develop certain cancerous conditions of the blood, particularly myelodysplastic syndrome or leukemia during adolescence. Some people with severe congenital neutropenia have additional health problems such as seizures, developmental delay, or heart and genital abnormalities.

Wikipedia : 74 Severe congenital neutropenia (SCN), also often known as Kostmann syndrome or disease, is a group of... more...

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Related Diseases for Severe Congenital Neutropenia

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Diseases in the Neutropenia family:

Neutropenia, Chronic Familial Neutropenia, Severe Congenital, 1, Autosomal Dominant
Neutropenia, Severe Congenital, 3, Autosomal Recessive Neutropenia, Severe Congenital, 4, Autosomal Recessive
Neutropenia, Severe Congenital, 2, Autosomal Dominant Neutropenia, Severe Congenital, 5, Autosomal Recessive
Neutropenia, Severe Congenital, 6, Autosomal Recessive Neutropenia, Severe Congenital, 7, Autosomal Recessive
Neutropenia, Severe Congenital, 8, Autosomal Dominant Severe Congenital Neutropenia
Severe Congenital Neutropenia 1 Elane-Related Neutropenia
Severe Congenital Neutropenia Autosomal Dominant Acquired Neutropenia
Autosomal Recessive Severe Congenital Neutropenia

Diseases related to Severe Congenital Neutropenia via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 237)
# Related Disease Score Top Affiliating Genes
1 severe congenital neutropenia autosomal dominant 34.6 SRP54 GFI1 ELANE
2 autosomal recessive severe congenital neutropenia 34.5 HAX1 G6PC3 ELANE CSF3R
3 neutropenia, severe congenital, 3, autosomal recessive 33.9 IL3 HAX1 ELANE CSF3R CSF3 CSF2
4 cohen syndrome 33.0 VPS45 JAGN1 HAX1 G6PC3
5 cyclic neutropenia 31.9 KITLG JAGN1 IL3 HAX1 GFI1 G6PC3
6 bacterial infectious disease 31.1 IL3 ELANE CSF3 CSF2 CAMP
7 granulocytopenia 30.7 IL3 CSF3 CSF2
8 myeloid leukemia 30.5 STAT5A PTPN11 JAK2 IL3 CSF3R CSF3
9 chronic neutrophilic leukemia 30.5 JAK2 CSF3R CSF3
10 whim syndrome 30.3 HAX1 G6PC3 ELANE CSF3
11 shwachman-diamond syndrome 1 30.3 SRP54 HAX1 G6PC3 ELANE CSF3R CSF3
12 neutropenia 30.2 WAS VPS45 SRP54 PTPN11 LEF1 KITLG
13 thrombocytopenia 30.2 WAS KITLG JAK2 IL3 CSF3 CSF2
14 pancytopenia 30.1 IL3 G6PC3 CSF3 CSF2
15 aplastic anemia 30.1 KITLG IL3 CSF3R CSF3 CSF2
16 myelofibrosis 30.1 VPS45 STAT5A JAK2 IL3 CSF3R CSF3
17 leukemia, acute myeloid 30.1 STAT5A PTPN11 KITLG JAK2 IL3 GFI1
18 acute leukemia 30.1 KITLG JAK2 IL3 CSF3R CSF3 CSF2
19 megakaryocytic leukemia 30.0 KITLG JAK2 IL3 CSF2
20 chronic myelomonocytic leukemia 30.0 STAT5A PTPN11 JAK2 CSF3R CSF3 CSF2
21 myelodysplastic syndrome 29.9 STAT5A PTPN11 KITLG JAK2 IL3 HAX1
22 leukemia, acute lymphoblastic 29.9 PTPN11 LEF1 KITLG JAK2 IL3 CSF3R
23 diamond-blackfan anemia 29.7 KITLG JAK2 IL3 CSF2
24 leukemia, chronic myeloid 28.7 STAT5A PTPN11 LEF1 KITLG JAK2 IL3
25 severe congenital neutropenia 1 12.7
26 autosomal recessive severe congenital neutropenia due to cxcr2 deficiency 12.4
27 neutropenia, severe congenital, x-linked 12.3
28 neutropenia, severe congenital, 7, autosomal recessive 12.1
29 neutropenia, severe congenital, 4, autosomal recessive 12.0
30 neutropenia, severe congenital, 5, autosomal recessive 12.0
31 neutropenia, severe congenital, 1, autosomal dominant 11.6
32 neutropenia, severe congenital, 8, autosomal dominant 11.6
33 neutropenia, severe congenital, 6, autosomal recessive 11.6
34 neutropenia, severe congenital, 2, autosomal dominant 11.5
35 neutropenia, lethal congenital, with eosinophilia 11.5
36 wiskott-aldrich syndrome 11.5
37 reticular dysgenesis 11.3
38 immunodeficiency due to defect in mapbp-interacting protein 11.1
39 large granular lymphocyte leukemia 10.5 CSF3 CSF2
40 elane-related neutropenia 10.5
41 g6pc3 deficiency 10.5
42 engraftment syndrome 10.5 CSF3 CSF2
43 amegakaryocytic thrombocytopenia, congenital 10.4 JAK2 IL3 HAX1
44 retinitis pigmentosa and erythrocytic microcytosis 10.4 JAK2 IL3 CSF3
45 eosinophilic gastroenteritis 10.4 IL3 CSF3 CSF2
46 gastroenteritis 10.4 IL3 CSF3 CSF2
47 myeloid and lymphoid neoplasms associated with pdgfra rearrangement 10.4 JAK2 CSF2
48 human t-cell leukemia virus type 2 10.4 STAT5A CSF2
49 sm-ahnmd 10.3 KITLG JAK2
50 autosomal recessive disease 10.3

Graphical network of the top 20 diseases related to Severe Congenital Neutropenia:



Diseases related to Severe Congenital Neutropenia
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Symptoms & Phenotypes for Severe Congenital Neutropenia

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GenomeRNAi Phenotypes related to Severe Congenital Neutropenia according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00221-A-2 9.68 JAK2
2 Decreased viability GR00249-S 9.68 BIRC5 CAMP CEBPE CSF2 CSF3R G6PC3
3 Decreased viability GR00381-A-1 9.68 BIRC5 CEBPE JAGN1
4 Decreased viability GR00386-A-1 9.68 BIRC5 CSF3 JAGN1 KITLG SRP54
5 Decreased viability GR00402-S-2 9.68 BIRC5 CEBPE G6PC3 IL3 LEF1 SRP54

MGI Mouse Phenotypes related to Severe Congenital Neutropenia:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 cellular MP:0005384 10.25 BIRC5 CAMP CEBPE CSF2 CSF3R GFI1
2 hematopoietic system MP:0005397 10.25 BIRC5 CAMP CEBPE CSF2 CSF3 CSF3R
3 immune system MP:0005387 10.19 BIRC5 CAMP CEBPE CSF2 CSF3 CSF3R
4 endocrine/exocrine gland MP:0005379 10.11 BIRC5 CSF2 G6PC3 GFI1 HAX1 JAK2
5 integument MP:0010771 9.81 CEBPE CSF2 CSF3 ELANE JAK2 KITLG
6 mortality/aging MP:0010768 9.8 BIRC5 CAMP CEBPE CSF2 CSF3R ELANE
7 neoplasm MP:0002006 9.1 CSF2 ELANE JAK2 KITLG PTPN11 WAS
Sources

Drugs & Therapeutics for Severe Congenital Neutropenia

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Drugs for Severe Congenital Neutropenia (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show top 50) (show all 55)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Anti-Infective Agents Phase 2, Phase 3
2 Antiviral Agents Phase 2, Phase 3
3 Anti-HIV Agents Phase 2, Phase 3
4 Anti-Retroviral Agents Phase 2, Phase 3
5 Plerixafor octahydrochloride Phase 2, Phase 3
6
Methotrexate Approved Phase 2 59-05-2, 1959-05-2 126941
7
leucovorin Approved Phase 2 58-05-9 6006 143
8
Clotrimazole Approved, Vet_approved Phase 2 23593-75-1 2812
9
Miconazole Approved, Investigational, Vet_approved Phase 2 22916-47-8 4189
10
Methylprednisolone Approved, Vet_approved Phase 1, Phase 2 83-43-2 6741
11
Methylprednisolone hemisuccinate Approved Phase 1, Phase 2 2921-57-5
12
Prednisolone phosphate Approved, Vet_approved Phase 1, Phase 2 302-25-0
13 Prednisolone acetate Approved, Vet_approved Phase 1, Phase 2 52-21-1
14
Prednisolone Approved, Vet_approved Phase 1, Phase 2 50-24-8 5755
15
Thiotepa Approved, Investigational Phase 1, Phase 2 52-24-4 5453
16
Tacrolimus Approved, Investigational Phase 1, Phase 2 104987-11-3 445643 439492 6473866
17
Cyclophosphamide Approved, Investigational Phase 1, Phase 2 50-18-0, 6055-19-2 2907
18
Sirolimus Approved, Investigational Phase 1, Phase 2 53123-88-9 5284616 6436030 46835353
19
Fludarabine Approved Phase 1, Phase 2 21679-14-1, 75607-67-9 30751
20
Melphalan Approved Phase 1, Phase 2 148-82-3 460612 4053
21
alemtuzumab Approved, Investigational Phase 1, Phase 2 216503-57-0
22
Busulfan Approved, Investigational Phase 1, Phase 2 55-98-1 2478
23
Folic acid Approved, Nutraceutical, Vet_approved Phase 2 59-30-3 6037
24
Prednisolone hemisuccinate Experimental Phase 1, Phase 2 2920-86-7
25 Dermatologic Agents Phase 2
26 Antimetabolites Phase 1, Phase 2
27 Antilymphocyte Serum Phase 1, Phase 2
28 Vitamin B Complex Phase 2
29 Antifungal Agents Phase 2
30 Folic Acid Antagonists Phase 2
31 Folate Phase 2
32 Cyclosporins Phase 2
33 Vitamin B9 Phase 2
34 Immunologic Factors Phase 1, Phase 2
35 Immunosuppressive Agents Phase 1, Phase 2
36 Alkylating Agents Phase 1, Phase 2
37 Gastrointestinal Agents Phase 1, Phase 2
38 Antineoplastic Agents, Immunological Phase 1, Phase 2
39 Methylprednisolone Acetate Phase 1, Phase 2
40 Hormones Phase 1, Phase 2
41 Neuroprotective Agents Phase 1, Phase 2
42 Hormone Antagonists Phase 1, Phase 2
43 Antiemetics Phase 1, Phase 2
44 glucocorticoids Phase 1, Phase 2
45 Calcineurin Inhibitors Phase 1, Phase 2
46 Protective Agents Phase 1, Phase 2
47 Antirheumatic Agents Phase 1, Phase 2
48 Anti-Inflammatory Agents Phase 1, Phase 2
49 Pharmaceutical Solutions Phase 1, Phase 2
50 Antineoplastic Agents, Hormonal Phase 1, Phase 2

Interventional clinical trials:

(show all 14)
# Name Status NCT ID Phase Drugs
1 A Phase III Double-Blind Randomized Crossover Study of Plerixafor Versus G-CSF in the Treatment of Patients With WHIM Syndrome. Active, not recruiting NCT02231879 Phase 2, Phase 3 Plerixafor;G-CSF
2 Phase I/II Trial Of Hematopoietic Stem Cell Transplant (HSCT) For Children With A Genetic Disease Of Blood Cells Without An HLA-Matched Sibling Donor Completed NCT00730314 Phase 1, Phase 2
3 Bone Marrow Stem Cell Transplantation for Children With Stem Cell Defects, Marrow Failure Syndromes, or Myeloid Leukemia in 1Remission Completed NCT00305708 Phase 1, Phase 2 busulfan;fludarabine phosphate
4 Evaluation of Fludarabine, Busulfan and Alemtuzumab as a Reduced Toxicity Ablative Bone Marrow Stem Cell Transplant Regimen for Children With Stem Cell Defects, Marrow Failure Syndromes, or Myelodysplastic Syndrome (MDS)/Leukemia Completed NCT00301834 Phase 2 busulfan;cyclosporine;fludarabine phosphate;methotrexate;methylprednisolone
5 CD34+ Stem Cell Selection for Patients Receiving a Matched or Partially Matched Family or Unrelated Adult Donor Allogeneic Stem Cell Transplant for Malignant Disease Recruiting NCT02061800 Phase 1, Phase 2 Thiotepa;Cyclophosphamide;Alemtuzumab;Tacrolimus;Melphalan;Busulfan;Fludarabine;Methylprednisolone
6 A Phase I Study of Mozobil (TM) in the Treatment of Patients With WHIMS Recruiting NCT00967785 Phase 1, Phase 2 Mozobil (TM)
7 CD34+ Stem Cell Selection for Patients Receiving a Matched or Partially Matched Family or Unrelated Adult Donor Allogeneic Stem Cell Transplantation for Non-Malignant Disease Active, not recruiting NCT01966367 Phase 1, Phase 2
8 Stem Cell Enriched, T Cell Depleted Haplocompatible Peripheral Blood Transplantation for Children With Myelodysplastic Disease, Leukemia, Marrow Failure Syndromes, or Severe Immunodeficiency Diseases Completed NCT00295971 Phase 1 fludarabine phosphate;thiotepa
9 A Phase 1B, Open-Label, Multicenter Study of Mavorixafor in Patients With Severe Congenital Neutropenia and Chronic Neutropenia Disorders Not yet recruiting NCT04154488 Phase 1 Mavorixafor
10 Investigation of Dental Health in Children With Neutrophil Defects: A Clinical Study Unknown status NCT03069079
11 Identification of the Molecular Bases of Syndromic Congenital Neutropenia With Development Anomalies Completed NCT02866162
12 Study of Allogeneic Bone Marrow Transplantation Using Matched, Related Donors in Patients With Nonmalignant Hematologic Disorders Completed NCT00005893 anti-thymocyte globulin;busulfan;cyclophosphamide
13 Etiologic Investigation of Cancer Susceptibility in Inherited Bone Marrow Failure Syndromes: A Natural History Study Recruiting NCT00027274
14 Alefacept and Allogeneic Hematopoietic Stem Cell Transplantation for Children With Non-Malignant Diseases Who Have Been Multiply Transfused: a Pilot Study Terminated NCT01319851 Alefacept

Search NIH Clinical Center for Severe Congenital Neutropenia

Cell-based therapeutics:


LifeMap Discovery
Data from LifeMap, the Embryonic Development and Stem Cells Database
Read about Severe Congenital Neutropenia cell therapies at LifeMap Discovery.
Stem-cell-based therapeutic approaches for Severe Congenital Neutropenia:
ALD-151, umbilical cord blood cells for hematologic and immunodefeciency diseases
Hematopoietic stem cells for refractory severe aplastic anemia or refractory cytopenias
Embryonic/Adult Cultured Cells Related to Severe Congenital Neutropenia:
Umbilical cord blood ALDH+ cells (ALD-151) PMIDs: 10430905
Peripheral blood-derived hematopoietic stem cells
Sources

Genetic Tests for Severe Congenital Neutropenia

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Genetic tests related to Severe Congenital Neutropenia:

# Genetic test Affiliating Genes
1 Severe Congenital Neutropenia 29
2 Congenital Neutropenia 29
Sources

Anatomical Context for Severe Congenital Neutropenia

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MalaCards organs/tissues related to Severe Congenital Neutropenia:

40
Neutrophil, Bone, Myeloid, Bone Marrow, Liver, Heart, Lung
Sources

Publications for Severe Congenital Neutropenia

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Articles related to Severe Congenital Neutropenia:

(show top 50) (show all 706)
# Title Authors PMID Year
1
Neutrophil elastase-processing defect in cyclic hematopoietic dogs. 61 54
19941936 2010
2
Prevalence of mutations in ELANE, GFI1, HAX1, SBDS, WAS and G6PC3 in patients with severe congenital neutropenia. 54 61
19775295 2009
3
Double de novo mutations of ELANE (ELA2) in a patient with severe congenital neutropenia requiring high-dose G-CSF therapy. 54 61
19694719 2009
4
Neutrophil elastase is severely down-regulated in severe congenital neutropenia independent of ELA2 or HAX1 mutations but dependent on LEF-1. 61 54
19620402 2009
5
Severe congenital neutropenia: a negative synergistic effect of multiple mutations of ELANE (ELA2) gene. 61 54
19594744 2009
6
Site-specific ubiquitination determines lysosomal sorting and signal attenuation of the granulocyte colony-stimulating factor receptor. 61 54
19453968 2009
7
A novel mutation Ala57Val of the ELA2 gene in a Korean boy with severe congenital neutropenia. 54 61
18946670 2009
8
Gfi1 integrates progenitor versus granulocytic transcriptional programming. 61 54
19346496 2009
9
Ela2 mutations and clinical manifestations in familial congenital neutropenia. 54 61
19415009 2009
10
Survivin expression in the bone marrow of patients with severe congenital neutropenia. 61 54
18818705 2009
11
Clinical implications of ELA2-, HAX1-, and G-CSF-receptor (CSF3R) mutations in severe congenital neutropenia. 61 54
19120359 2009
12
Genetic and molecular diagnosis of severe congenital neutropenia. 61 54
19057199 2009
13
A patient with glycogen storage disease type Ib presenting with acute myeloid leukemia (AML) bearing monosomy 7 and translocation t(3;8)(q26;q24) after 14 years of treatment with granulocyte colony-stimulating factor (G-CSF): a case report. 54 61
18826620 2008
14
Transformation of severe congenital neutropenia to early acute lymphoblastic leukemia in a patient with HAX1 mutation and without G-CSF administration or receptor mutation. 61 54
18354489 2008
15
Functional interaction between mutations in the granulocyte colony-stimulating factor receptor in severe congenital neutropenia. 61 54
18513286 2008
16
Csf3r mutations in mice confer a strong clonal HSC advantage via activation of Stat5. 61 54
18292815 2008
17
Chronic idiopathic neutropenias and severe congenital neutropenia. 61 54
18043240 2008
18
Severe congenital neutropenia and the unfolded protein response. 61 54
18043239 2008
19
Neutrophil elastase mutations and risk of leukaemia in severe congenital neutropenia. 61 54
18028488 2008
20
G-CSFR ubiquitination critically regulates myeloid cell survival and proliferation. 61 54
18923646 2008
21
Mutations of the ELA2 gene found in patients with severe congenital neutropenia induce the unfolded protein response and cellular apoptosis. 54 61
17761833 2007
22
Genetic heterogeneity in severe congenital neutropenia: how many aberrant pathways can kill a neutrophil? 54 61
17989524 2007
23
Double de novo mutations of ELA2 in cyclic and severe congenital neutropenia. 61 54
17436313 2007
24
LEF-1 is a decisive transcription factor in neutrophil granulopoiesis. 61 54
17360796 2007
25
G-CSF treatment of severe congenital neutropenia reverses neutropenia but does not correct the underlying functional deficiency of the neutrophil in defending against microorganisms. 54 61
17311988 2007
26
Neutrophil elastase in cyclic and severe congenital neutropenia. 61 54
17053055 2007
27
Current diagnosis of inherited bone marrow failure syndromes. 54 61
17454774 2007
28
The role of the granulocyte colony-stimulating factor receptor (G-CSF-R) in disease. 61 54
17127322 2007
29
Incidence of CSF3R mutations in severe congenital neutropenia and relevance for leukemogenesis: Results of a long-term survey. 54 61
16985178 2007
30
Molecular screening of the neutrophil elastase gene in congenital neutropenia. 61 54
17202606 2006
31
A family of severe congenital neutropenia with -199C to A substitution in ELA2 promoter. 61 54
16795059 2006
32
Src family kinases are important negative regulators of G-CSF-dependent granulopoiesis. 61 54
16772601 2006
33
Granulocyte colony-stimulating factor preferentially stimulates proliferation of monosomy 7 cells bearing the isoform IV receptor. 61 54
16980411 2006
34
The growth factor independence-1 transcription factor: new functions and new insights. 61 54
16716599 2006
35
The Severe Chronic Neutropenia International Registry: 10-Year Follow-up Report. 61 54
18632498 2006
36
The incidence of leukemia and mortality from sepsis in patients with severe congenital neutropenia receiving long-term G-CSF therapy. 61 54
16497969 2006
37
Malignant myeloid transformation in a child with severe congenital neutropenia (Kostmann's syndrome). 61 54
16898320 2006
38
Strong evidence for autosomal dominant inheritance of severe congenital neutropenia associated with ELA2 mutations. 61 54
16737875 2006
39
Neutrophil elastase and granulocyte colony-stimulating factor receptor mutation analyses and leukemia evolution in severe congenital neutropenia patients belonging to the original Kostmann family in northern Sweden. 54 61
16670064 2006
40
Periodontal disease in patients from the original Kostmann family with severe congenital neutropenia. 54 61
16584360 2006
41
Increased CCAAT enhancer-binding protein epsilon (C/EBPepsilon) expression and premature apoptosis in myeloid cells expressing Gfi-1 N382S mutant associated with severe congenital neutropenia. 54 61
16500901 2006
42
A novel mutation in the juxtamembrane intracellular sequence of the granulocyte colony-stimulating factor (G-CSF) receptor gene in a patient with severe congenital neutropenia augments GCSF proliferation activity but not through the MAP kinase cascade. 61 54
16229088 2005
43
Aberrant subcellular targeting of the G185R neutrophil elastase mutant associated with severe congenital neutropenia induces premature apoptosis of differentiating promyelocytes. 61 54
15657182 2005
44
Heterogeneous expression pattern of pro- and anti-apoptotic factors in myeloid progenitor cells of patients with severe congenital neutropenia treated with granulocyte colony-stimulating factor. 54 61
15813856 2005
45
Novel mechanism of G-CSF refractoriness in patients with severe congenital neutropenia. 54 61
15353486 2005
46
Analysis of risk factors for myelodysplasias, leukemias and death from infection among patients with congenital neutropenia. Experience of the French Severe Chronic Neutropenia Study Group. 61 54
15642668 2005
47
Autosomal-dominant primary immunodeficiencies. 54 61
15604887 2005
48
Congenital neutropenia: advances in diagnosis and treatment. 54 61
15640692 2004
49
Loss of SHIP and CIS recruitment to the granulocyte colony-stimulating factor receptor contribute to hyperproliferative responses in severe congenital neutropenia/acute myelogenous leukemia. 61 54
15470047 2004
50
Efficacy and safety of two different rG-CSF preparations in the treatment of patients with severe congenital neutropenia. 61 54
15198743 2004
Sources

Variations for Severe Congenital Neutropenia

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ClinVar genetic disease variations for Severe Congenital Neutropenia:

6 (show top 50) (show all 62) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 JAGN1 NM_032492.4(JAGN1):c.3G>A (p.Met1Ile)SNV Pathogenic 156113 rs587777727 3:9932409-9932409 3:9890725-9890725
2 JAGN1 NM_032492.4(JAGN1):c.130C>T (p.His44Tyr)SNV Pathogenic 156114 rs587777728 3:9934639-9934639 3:9892955-9892955
3 JAGN1 NM_032492.4(JAGN1):c.485A>G (p.Gln162Arg)SNV Pathogenic 156116 rs587777730 3:9934994-9934994 3:9893310-9893310
4 JAGN1 NM_032492.4(JAGN1):c.35_43del (p.Thr12_Gly14del)deletion Pathogenic 156117 rs587777731 3:9932436-9932444 3:9890752-9890760
5 CSF3R NM_000760.4(CSF3R):c.922C>T (p.Arg308Cys)SNV Pathogenic 161982 rs606231473 1:36937914-36937914 1:36472313-36472313
6 JAGN1 NM_032492.4(JAGN1):c.40G>A (p.Gly14Ser)SNV Pathogenic 190480 rs786205704 3:9932446-9932446 3:9890762-9890762
7 JAGN1 NM_032492.4(JAGN1):c.59G>A (p.Arg20Gln)SNV Pathogenic 190479 rs777966677 3:9932465-9932465 3:9890781-9890781
8 JAGN1 NM_032492.4(JAGN1):c.297C>G (p.Tyr99Ter)SNV Pathogenic 190481 rs786205705 3:9934806-9934806 3:9893122-9893122
9 CSF3R NM_000760.4(CSF3R):c.340C>T (p.Gln114Ter)SNV Likely pathogenic 812885 1:36940999-36940999 1:36475398-36475398
10 CSF3R NM_000760.4(CSF3R):c.1576+1G>ASNV Likely pathogenic 812884 1:36934756-36934756 1:36469155-36469155
11 TCIRG1 NM_006019.4(TCIRG1):c.2206C>A (p.Arg736Ser)SNV Conflicting interpretations of pathogenicity 127173 rs587779413 11:67817691-67817691 11:68050224-68050224
12 JAGN1 NM_032492.4(JAGN1):c.63G>T (p.Glu21Asp)SNV Conflicting interpretations of pathogenicity 156115 rs587777729 3:9932469-9932469 3:9890785-9890785
13 GFI1 NM_005263.5(GFI1):c.925-40CT[17]short repeat Conflicting interpretations of pathogenicity 298182 rs35896485 1:92944315-92944316 1:92478758-92478759
14 GFI1 NM_005263.5(GFI1):c.925-40CT[20]short repeat Conflicting interpretations of pathogenicity 298179 rs35896485 1:92944314-92944315 1:92478757-92478758
15 GFI1 NM_005263.5(GFI1):c.925-40CT[23]short repeat Conflicting interpretations of pathogenicity 298183 rs35896485 1:92944314-92944315 1:92478757-92478758
16 GFI1 NM_005263.5(GFI1):c.925-40CT[16]short repeat Conflicting interpretations of pathogenicity 298184 rs35896485 1:92944315-92944318 1:92478758-92478761
17 GFI1 NM_005263.5(GFI1):c.925-40CT[13]short repeat Conflicting interpretations of pathogenicity 298186 rs35896485 1:92944315-92944324 1:92478758-92478767
18 GFI1 NM_005263.5(GFI1):c.925-40CT[25]short repeat Conflicting interpretations of pathogenicity 298181 rs35896485 1:92944314-92944315 1:92478757-92478758
19 GFI1 NM_005263.5(GFI1):c.925-40CT[22]short repeat Conflicting interpretations of pathogenicity 298180 rs35896485 1:92944314-92944315 1:92478757-92478758
20 GFI1 NM_005263.5(GFI1):c.-174C>TSNV Uncertain significance 298194 rs886046557 1:92952357-92952357 1:92486800-92486800
21 GFI1 NM_005263.5(GFI1):c.925-7_925-6insTCTCTTinsertion Uncertain significance 298187 rs766365921 1:92944316-92944317 1:92478759-92478760
22 GFI1 NM_005263.5(GFI1):c.*255C>TSNV Uncertain significance 298174 rs886046554 1:92941331-92941331 1:92475774-92475774
23 G6PC3 NM_138387.3(G6PC3):c.-191T>GSNV Uncertain significance 323455 rs886052984 17:42148143-42148143 17:44070775-44070775
24 G6PC3 NM_138387.3(G6PC3):c.*1_*3CTT[1]short repeat Uncertain significance 323471 rs761219348 17:42153412-42153414 17:44076044-44076046
25 GFI1 NM_005263.5(GFI1):c.588C>T (p.Gly196=)SNV Uncertain significance 298189 rs370716261 1:92946356-92946356 1:92480799-92480799
26 GFI1 NM_005263.5(GFI1):c.311C>T (p.Ser104Leu)SNV Uncertain significance 298190 rs886046556 1:92946633-92946633 1:92481076-92481076
27 GFI1 NM_005263.5(GFI1):c.*1094G>ASNV Uncertain significance 298159 rs886046550 1:92940492-92940492 1:92474935-92474935
28 GFI1 NM_005263.5(GFI1):c.*822C>GSNV Uncertain significance 298165 rs1048968 1:92940764-92940764 1:92475207-92475207
29 GFI1 NM_005263.5(GFI1):c.*803C>TSNV Uncertain significance 298166 rs886046553 1:92940783-92940783 1:92475226-92475226
30 GFI1 NM_005263.5(GFI1):c.*1045T>CSNV Uncertain significance 298160 rs886046551 1:92940541-92940541 1:92474984-92474984
31 GFI1 NM_005263.5(GFI1):c.*912T>CSNV Uncertain significance 298162 rs886046552 1:92940674-92940674 1:92475117-92475117
32 HAX1 NM_006118.3(HAX1):c.-53deldeletion Likely benign 292701 rs373592376 1:154245143-154245143 1:154272667-154272667
33 GFI1 NM_005263.5(GFI1):c.319C>G (p.Pro107Ala)SNV Likely benign 259703 rs149914857 1:92946625-92946625 1:92481068-92481068
34 GFI1 NM_005263.5(GFI1):c.*407G>ASNV Likely benign 298171 rs545137392 1:92941179-92941179 1:92475622-92475622
35 GFI1 NM_005263.5(GFI1):c.1032C>T (p.Tyr344=)SNV Likely benign 298178 rs139144506 1:92944203-92944203 1:92478646-92478646
36 GFI1 NM_005263.5(GFI1):c.*992A>GSNV Likely benign 298161 rs116093836 1:92940594-92940594 1:92475037-92475037
37 GFI1 NM_005263.5(GFI1):c.*885G>ASNV Likely benign 298163 rs565374347 1:92940701-92940701 1:92475144-92475144
38 GFI1 NM_005263.5(GFI1):c.*881G>ASNV Likely benign 298164 rs538383914 1:92940705-92940705 1:92475148-92475148
39 GFI1 NM_005263.5(GFI1):c.-54G>TSNV Likely benign 298191 rs139390290 1:92949098-92949098 1:92483541-92483541
40 GFI1 NM_005263.5(GFI1):c.-90G>CSNV Likely benign 298192 rs565821550 1:92949134-92949134 1:92483577-92483577
41 GFI1 NM_005263.5(GFI1):c.-209G>ASNV Likely benign 298195 rs181163165 1:92952392-92952392 1:92486835-92486835
42 GFI1 NM_005263.5(GFI1):c.*597G>ASNV Likely benign 298169 rs549168199 1:92940989-92940989 1:92475432-92475432
43 GFI1 NM_005263.5(GFI1):c.*378C>GSNV Likely benign 298172 rs189400817 1:92941208-92941208 1:92475651-92475651
44 GFI1 NM_005263.5(GFI1):c.*315A>GSNV Likely benign 298173 rs191572929 1:92941271-92941271 1:92475714-92475714
45 GFI1 NM_005263.5(GFI1):c.*1239T>CSNV Likely benign 298155 rs7514362 1:92940347-92940347 1:92474790-92474790
46 GFI1 NM_005263.5(GFI1):c.-99-7C>GSNV Likely benign 298193 rs540674112 1:92949150-92949150 1:92483593-92483593
47 GFI1 NM_005263.5(GFI1):c.*215G>ASNV Likely benign 298176 rs41300327 1:92941371-92941371 1:92475814-92475814
48 GFI1 NM_005263.5(GFI1):c.1188C>T (p.Phe396=)SNV Benign/Likely benign 298177 rs374783582 1:92941667-92941667 1:92476110-92476110
49 GFI1 NM_005263.5(GFI1):c.792C>T (p.Phe264=)SNV Benign/Likely benign 298188 rs114487177 1:92946037-92946037 1:92480480-92480480
50 GFI1 NM_005263.5(GFI1):c.168C>T (p.Ser56=)SNV Benign/Likely benign 259702 rs143913803 1:92948551-92948551 1:92482994-92482994
Sources

Expression for Severe Congenital Neutropenia

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Search GEO for disease gene expression data for Severe Congenital Neutropenia.
Sources

Pathways for Severe Congenital Neutropenia

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Pathways related to Severe Congenital Neutropenia according to GeneCards Suite gene sharing:

(show all 31)
# Super pathways Score Top Affiliating Genes
1
Innate Immune System 65
Show member pathways
 13.9 WAS STAT5A PTPN11 KITLG JAK2 IL3
2
Akt Signaling 63
Show member pathways
 13.29 WAS STAT5A KITLG JAK2 IL3 CSF3R
3
Cytokine Signaling in Immune system 65
Show member pathways
 13.24 STAT5A PTPN11 KITLG JAK2 IL3 CSF3R
4
PAK Pathway 63
Show member pathways
 13.09 WAS PTPN11 LEF1 KITLG JAK2 IL3
5
PI3K-Akt signaling pathway 36
Show member pathways
 12.9 KITLG JAK2 IL3 G6PC3 CSF3R CSF3
6
Endometrial cancer 36
Show member pathways
 12.72 STAT5A PTPN11 LEF1 IL3 CSF2 CEBPE
7
Pathways in cancer 36
12.67 STAT5A LEF1 KITLG JAK2 IL3 CSF3R
8
NF-kappaB Signaling 4
12.46 STAT5A KITLG JAK2 IL3
9
Immune response Role of DAP12 receptors in NK cells 22
Show member pathways
 12.41 WAS PTPN11 IL3 CSF2
10
Development IGF-1 receptor signaling 22
Show member pathways
 12.31 STAT5A PTPN11 JAK2 BIRC5
11
Transcriptional misregulation in cancer 36
12.18 IL3 ELANE CSF2 CEBPE
12
Kit receptor signaling pathway 1
Show member pathways
 12.06 STAT5A PTPN11 KITLG JAK2 IL3
13
G beta-gamma signalling through PI3Kgamma 65
Show member pathways
 12.03 PTPN11 JAK2 IL3 CSF2
14
JAK-STAT signaling pathway 36
Show member pathways
 11.9 STAT5A PTPN11 JAK2 IL3 CSF3R CSF3
15
Development EPO-induced Jak-STAT pathway 22
Show member pathways
 11.8 STAT5A PTPN11 JAK2
16
Visual Cycle in Retinal Rods 63
11.79 STAT5A PTPN11 JAK2
17
Cytokine production by Th17 cells in CF (Mouse model) 22
Show member pathways
 11.77 JAK2 CSF3 CSF2
18
Hematopoietic Stem Cells and Lineage-specific Markers 64
11.72 KITLG IL3 CSF3R CSF3 CSF2
19
C-MYB transcription factor network 1
11.69 LEF1 KITLG ELANE
20
CXCR4-mediated signaling events 1
11.67 STAT5A PTPN11 JAK2
21
Immune response IL-2 activation and signaling pathway 22
Show member pathways
 11.65 STAT5A PTPN11 JAK2 IL3
22
Adipocytokine signaling pathway 36
11.62 PTPN11 JAK2 G6PC3
23
Hematopoietic cell lineage 36
11.55 KITLG IL3 CSF3R CSF3 CSF2
24
Hepatitis C and Hepatocellular Carcinoma 1
11.47 PTPN11 LEF1 BIRC5
25
Thymic Stromal LymphoPoietin (TSLP) Signaling Pathway 1
11.42 STAT5A PTPN11 JAK2
26
Th2 Differentiation 64
11.41 STAT5A JAK2 GFI1
27
Interleukin-11 Signaling Pathway 1
11.38 PTPN11 JAK2 BIRC5
28
Growth hormone receptor signaling 65
Show member pathways
 11.3 STAT5A PTPN11 JAK2
29
Cytokines and Inflammatory Response 1
11.13 IL3 CSF3 CSF2
30
Immune response_Oncostatin M signaling via JAK-Stat in human cells 22
10.93 STAT5A JAK2
31
Hematopoietic Stem Cell Differentiation 1
10.7 STAT5A KITLG IL3 CSF3 CSF2
Sources

GO Terms for Severe Congenital Neutropenia

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Biological processes related to Severe Congenital Neutropenia according to GeneCards Suite gene sharing:

(show all 19)
# Name GO ID Score Top Affiliating Genes
1 positive regulation of transcription by RNA polymerase II GO:0045944 10.04 WAS STAT5A LEF1 HAX1 GFI1 CSF3
2 MAPK cascade GO:0000165 9.85 KITLG JAK2 IL3 CSF2
3 cellular response to lipopolysaccharide GO:0071222 9.83 GFI1 CSF3 CSF2 CEBPE CAMP
4 defense response GO:0006952 9.77 WAS STAT5A CSF3R CEBPE CAMP
5 positive regulation of protein kinase B signaling GO:0051897 9.76 PTPN11 KITLG HAX1 CSF3
6 positive regulation of cell proliferation GO:0008284 9.76 LEF1 KITLG JAK2 IL3 CSF3 CSF2
7 positive regulation of phosphatidylinositol 3-kinase signaling GO:0014068 9.71 JAK2 HAX1 CSF3
8 cellular response to cytokine stimulus GO:0071345 9.71 PTPN11 LEF1 HAX1 CSF3
9 positive regulation of tyrosine phosphorylation of STAT protein GO:0042531 9.69 JAK2 IL3 CSF2
10 positive regulation of actin cytoskeleton reorganization GO:2000251 9.58 HAX1 CSF3
11 interleukin-6-mediated signaling pathway GO:0070102 9.58 PTPN11 JAK2
12 embryonic hemopoiesis GO:0035162 9.57 KITLG IL3
13 JAK-STAT cascade involved in growth hormone signaling pathway GO:0060397 9.56 STAT5A JAK2
14 regulation of myeloid cell differentiation GO:0045637 9.52 CSF3R CSF2
15 granulocyte differentiation GO:0030851 9.5 SRP54 CSF3 CEBPE
16 positive regulation of granulocyte differentiation GO:0030854 9.48 LEF1 HAX1
17 neutrophil differentiation GO:0030223 9.43 LEF1 JAGN1 CSF2
18 positive regulation of peptidyl-tyrosine phosphorylation GO:0050731 9.43 PTPN11 KITLG JAK2 IL3 HAX1 CSF3
19 cytokine-mediated signaling pathway GO:0019221 9.23 STAT5A PTPN11 JAK2 IL3 CSF3R CSF3

Molecular functions related to Severe Congenital Neutropenia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cytokine activity GO:0005125 9.46 KITLG IL3 CSF3 CSF2
2 phospholipase binding GO:0043274 9.32 WAS PTPN11
3 insulin receptor substrate binding GO:0043560 9.26 PTPN11 JAK2
4 peptide hormone receptor binding GO:0051428 8.96 PTPN11 JAK2
5 growth factor activity GO:0008083 8.92 KITLG IL3 CSF3 CSF2
Sources

Sources for Severe Congenital Neutropenia

About this section
3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
The MalaCards human disease database index: 1-9 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
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