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MCID: SVR003
MIFTS: 58

Severe Congenital Neutropenia

Categories: Blood diseases, Bone diseases, Genetic diseases, Immune diseases, Rare diseases
Genes Variations Tissues Related diseases Publications Pathways Drugs
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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 38 12 53 25 29 6 15 73
Congenital Neutropenia 25 29 6
Severe Infantile Genetic Neutropenia 25
Infantile Genetic Agranulocytosis 25
Neutropenia, Severe Congenital 55
Congenital Agranulocytosis 25
Kostmann's Agranulocytosis 25
Kostmann's Syndrome 25
Kostmanns Syndrome 55
Kostmann Disease 25

Classifications:

MalaCards categories:
Global: Rare diseases Genetic diseases
Anatomical: Blood diseases Bone diseases Immune diseases
See all MalaCards categories (disease lists)
ICD10: 33


External Ids:

Disease Ontology 12 DOID:0050590
ICD10 33 D70
UMLS 73 C1853118
Sources

Summaries for Severe Congenital Neutropenia

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NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 42738Disease definitionSevere congenital neutropenia is an immunodeficiency characterized by low levels of granulocytes (EpidemiologyThe prevalence in the general population is estimated at 1-1.7/333,300. Annual incidence is around 1/250,000 births.Clinical descriptionThis 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.EtiologyTo 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 methodsThe 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 diagnosisOn 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 diagnosisPrenatal diagnosis may be offered if the genotype is known.Genetic counselingThe 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 treatmentAll febrile episodes or infections should be reviewed by a hospital and treated actively. Prophylacticantibiotics 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 20µg/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.PrognosisThe 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 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 Busulfan and Vidarabine have been mentioned in the context of this disorder. Affiliated tissues include neutrophil, bone and myeloid, and related phenotypes are cellular and hematopoietic system

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.

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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
Severe Congenital Neutropenia Elane-Related Neutropenia
Severe Congenital Neutropenia Autosomal Dominant

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

(show top 50) (show all 105)
# Related Disease Score Top Affiliating Genes
1 severe congenital neutropenia autosomal dominant 34.1 ELANE GFI1
2 neutropenia 30.2 CSF2 CSF3 CSF3R ELANE G6PC3 GFI1
3 leukemia 30.2 CSF2 CSF3R JAK2 PTPN11
4 chronic neutrophilic leukemia 30.1 CSF3 CSF3R
5 granulocytopenia 29.8 CSF2 CSF3 IL3
6 myeloid leukemia 29.6 CSF2 CSF3R IL3 JAK2 PTPN11
7 pancytopenia 29.6 CSF2 CSF3 IL3
8 cyclic neutropenia 29.5 CSF2 CSF3 ELANE G6PC3 IL3 KITLG
9 myelofibrosis 29.5 CSF3 IL3 JAK2
10 chronic myelomonocytic leukemia 29.2 CSF2 CSF3R JAK2 PTPN11
11 aplastic anemia 29.0 CSF2 CSF3 CSF3R IL3 KITLG
12 leukemia, acute myeloid 29.0 CSF2 CSF3 CSF3R GFI1 IL3 JAK2
13 myelodysplastic syndrome 28.1 BIRC5 CSF2 CSF3 CSF3R IL3 JAK2
14 neutropenia, severe congenital, 3, autosomal recessive 12.3
15 autosomal recessive severe congenital neutropenia due to cxcr2 deficiency 12.2
16 neutropenia, severe congenital, x-linked 12.2
17 neutropenia, severe congenital, 5, autosomal recessive 11.8
18 neutropenia, severe congenital, 7, autosomal recessive 11.8
19 neutropenia, severe congenital, 6, autosomal recessive 11.4
20 neutropenia, lethal congenital, with eosinophilia 11.4
21 neutropenia, severe congenital, 4, autosomal recessive 11.4
22 neutropenia, severe congenital, 2, autosomal dominant 11.4
23 wiskott-aldrich syndrome 11.3
24 neutropenia, severe congenital, 1, autosomal dominant 11.2
25 reticular dysgenesis 11.2
26 dentin dysplasia, type i 11.1
27 cohen syndrome 11.0
28 hermansky-pudlak syndrome 2 11.0
29 immunodeficiency due to defect in mapbp-interacting protein 11.0
30 hematopoietic stem cell transplantation 10.2
31 osteoporosis 10.1
32 leukemia, acute lymphoblastic 10.1
33 lymphocytic leukemia 10.1
34 engraftment syndrome 10.1 CSF2 CSF3
35 capillary leak syndrome 10.1 CSF2 ELANE
36 trichosporonosis 10.1 CSF2 CSF3
37 seborrheic infantile dermatitis 10.1 CSF2 IL3
38 g6pc3 deficiency 10.0
39 chickenpox 10.0 JAGN1 VPS45
40 aggressive systemic mastocytosis 10.0 KITLG PTPN11
41 bacterial infectious disease 10.0 CSF2 CSF3 ELANE
42 acute basophilic leukemia 10.0
43 myelophthisic anemia 10.0 JAK2 PTPN11
44 mastoiditis 9.9
45 ewing's family of tumors 9.9 CSF3 KITLG
46 felty syndrome 9.9 CSF2 CSF3 IL3
47 leukocyte disease 9.9 CSF2 CSF3 IL3
48 retinitis pigmentosa and erythrocytic microcytosis 9.9 IL3 JAK2
49 acute lymphocytic leukemia 9.9
50 acute promyelocytic leukemia 9.9 CSF3 CSF3R ELANE IL3

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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MGI Mouse Phenotypes related to Severe Congenital Neutropenia:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 cellular MP:0005384 10.07 BIRC5 CSF2 CSF3R GFI1 HAX1 JAGN1
2 hematopoietic system MP:0005397 10.07 BIRC5 CSF2 CSF3 CSF3R ELANE G6PC3
3 endocrine/exocrine gland MP:0005379 10.02 BIRC5 CSF2 CSF3R G6PC3 GFI1 HAX1
4 immune system MP:0005387 9.97 BIRC5 CSF2 CSF3 CSF3R ELANE G6PC3
5 mortality/aging MP:0010768 9.65 BIRC5 CSF2 CSF3R ELANE G6PC3 GFI1
6 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 68)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Busulfan Approved, Investigational Phase 2, Phase 3,Phase 3,Phase 1,Not Applicable,Early Phase 1 55-98-1 2478
2
Vidarabine Approved, Investigational Phase 2, Phase 3,Phase 3,Early Phase 1 24356-66-9 32326 21704
3
Fludarabine Approved Phase 2, Phase 3,Phase 3,Phase 1,Not Applicable,Early Phase 1 75607-67-9, 21679-14-1 30751
4
Cyclophosphamide Approved, Investigational Phase 2, Phase 3,Phase 1,Not Applicable,Early Phase 1 6055-19-2, 50-18-0 2907
5
alemtuzumab Approved, Investigational Phase 2, Phase 3,Phase 1,Early Phase 1,Not Applicable 216503-57-0
6
Lenograstim Approved, Investigational Phase 2, Phase 3 135968-09-1
7 Immunologic Factors Phase 2, Phase 3,Phase 3,Phase 1,Not Applicable,Early Phase 1
8 Antimetabolites, Antineoplastic Phase 2, Phase 3,Phase 3,Phase 1,Early Phase 1
9 Alkylating Agents Phase 2, Phase 3,Phase 3,Phase 1,Not Applicable,Early Phase 1
10 Immunosuppressive Agents Phase 2, Phase 3,Phase 3,Phase 1,Not Applicable,Early Phase 1
11 Antineoplastic Agents, Alkylating Phase 2, Phase 3,Phase 3,Phase 1,Not Applicable,Early Phase 1
12 Antiviral Agents Phase 2, Phase 3,Phase 3,Early Phase 1
13 Antimetabolites Phase 2, Phase 3,Phase 3,Phase 1,Early Phase 1
14 Antilymphocyte Serum Phase 2, Phase 3,Phase 3,Phase 1,Not Applicable
15 Anti-Infective Agents Phase 2, Phase 3,Phase 3,Early Phase 1
16 Antirheumatic Agents Phase 2, Phase 3,Phase 1,Not Applicable,Early Phase 1
17 Adjuvants, Immunologic Phase 2, Phase 3
18
Prednisolone Approved, Vet_approved Phase 2,Phase 1 50-24-8 5755
19
leucovorin Approved Phase 2 58-05-9 6006 143
20
Methylprednisolone Approved, Vet_approved Phase 2,Phase 1 83-43-2 6741
21
Methylprednisolone hemisuccinate Approved Phase 2,Phase 1 2921-57-5
22
Methotrexate Approved Phase 2 59-05-2, 1959-05-2 126941
23
Prednisolone phosphate Approved, Vet_approved Phase 2,Phase 1 302-25-0
24
Miconazole Approved, Investigational, Vet_approved Phase 2 22916-47-8 4189
25
Thiotepa Approved, Investigational Phase 1, Phase 2,Not Applicable 52-24-4 5453
26
Melphalan Approved Phase 1, Phase 2,Phase 2,Not Applicable,Early Phase 1 148-82-3 4053 460612
27
Mycophenolic acid Approved Phase 2,Phase 1,Not Applicable 24280-93-1 446541
28
Tacrolimus Approved, Investigational Phase 1, Phase 2,Phase 2 104987-11-3 445643 439492
29
Sirolimus Approved, Investigational Phase 1, Phase 2 53123-88-9 46835353 6436030 5284616
30
Mechlorethamine Approved, Investigational Phase 2 51-75-2 4033
31
Folic Acid Approved, Nutraceutical, Vet_approved Phase 2 59-30-3 6037
32
Prednisolone hemisuccinate Experimental Phase 2,Phase 1 2920-86-7
33 Hormones Phase 2,Phase 1
34 Hormones, Hormone Substitutes, and Hormone Antagonists Phase 2,Phase 1
35 Nucleic Acid Synthesis Inhibitors Phase 2
36 Antineoplastic Agents, Hormonal Phase 2,Phase 1
37 Calcineurin Inhibitors Phase 2,Phase 1
38 Peripheral Nervous System Agents Phase 2,Phase 1
39 Antifungal Agents Phase 2
40 Vitamin B Complex Phase 2
41 Anti-Inflammatory Agents Phase 2,Phase 1
42 Folic Acid Antagonists Phase 2
43 Methylprednisolone acetate Phase 2,Phase 1
44 Folate Phase 2
45 Gastrointestinal Agents Phase 2,Phase 1
46 Prednisolone acetate Phase 2,Phase 1
47 Hormone Antagonists Phase 2,Phase 1
48 Antiemetics Phase 2,Phase 1
49 Neuroprotective Agents Phase 2,Phase 1
50 Cyclosporins Phase 2,Phase 1

Interventional clinical trials:

(show all 19)
# Name Status NCT ID Phase Drugs
1 Stem Cell Transplant for Bone Marrow Failure Syndromes Completed NCT00176878 Phase 2, Phase 3 Fludarabine monophosphate;Busulfan
2 Stem Cell Transplant for Hemoglobinopathy Active, not recruiting NCT00176852 Phase 2, Phase 3 Busulfan, Fludarabine, ATG, TLI;Busulfan, Cyclophosphamide, ATG, GCSF;Campath, Fludarabine, Cyclophosphamide
3 Unrelated Hematopoietic Stem Cell Transplantation(HSCT) for Genetic Diseases of Blood Cells Completed NCT00730314 Phase 1, Phase 2
4 Alemtuzumab, Fludarabine, and Busulfan Followed By Donor Stem Cell Transplant in Treating Young Patients With Hematologic Disorders Completed NCT00301834 Phase 2 busulfan;cyclosporine;fludarabine phosphate;methotrexate;methylprednisolone
5 Busulfan, Antithymocyte Globulin, and Fludarabine Followed By a Donor Stem Cell Transplant in Treating Young Patients With Blood Disorders, Bone Marrow Disorders, Chronic Myelogenous Leukemia in First Chronic Phase, or Acute Myeloid Leukemia in First Remission Completed NCT00305708 Phase 1, Phase 2 busulfan;fludarabine phosphate
6 Fludarabine Phosphate, Cyclophosphamide, Total Body Irradiation, and Donor Stem Cell Transplant in Treating Patients With Blood Cancer Recruiting NCT03333486 Phase 2 Cyclophosphamide;Fludarabine Phosphate
7 CD34+ (Malignant) Stem Cell Selection for Patients Receiving Allogenic Stem Cell Transplant Recruiting NCT02061800 Phase 1, Phase 2 Thiotepa;Cyclophosphamide;Alemtuzumab;Tacrolimus;Melphalan;Busulfan;Fludarabine;Methylprednisolone
8 Fludarabine Phosphate, Melphalan, and Low-Dose Total-Body Irradiation Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies Active, not recruiting NCT01529827 Phase 2 fludarabine phosphate;melphalan;tacrolimus;mycophenolate mofetil;methotrexate
9 Donor Stem Cell Transplant in Treating Young Patients With Myelodysplastic Syndrome, Leukemia, Bone Marrow Failure Syndrome, or Severe Immunodeficiency Disease Completed NCT00295971 Phase 1 fludarabine phosphate;thiotepa
10 BMT Abatacept for Non-Malignant Diseases Active, not recruiting NCT01917708 Phase 1 Abatacept
11 Screening for Genes in Patients With Congenital Neutropenia Completed NCT02866162
12 Partially Matched Stem Cell Transplantation for Patients With Refractory Severe Aplastic Anemia or Refractory Cytopenias Completed NCT00244010 Not Applicable
13 Study of Allogeneic Bone Marrow Transplantation Using Matched, Related Donors in Patients With Nonmalignant Hematologic Disorders Completed NCT00005893 Not Applicable anti-thymocyte globulin;busulfan;cyclophosphamide
14 Cancer in Inherited Bone Marrow Failure Syndromes Recruiting NCT00027274
15 CD34+ (Non-Malignant) Stem Cell Selection for Patients Receiving Allogeneic Stem Cell Transplantation Recruiting NCT01966367 Early Phase 1
16 Fludarabine Based RIC for Bone Marrow Failure Syndromes Recruiting NCT02928991 Early Phase 1
17 Investigation of the Genetics of Hematologic Diseases Recruiting NCT02720679
18 Hematopoietic Stem Cell Transplant for High Risk Hemoglobinopathies Recruiting NCT02179359 Not Applicable Reduced Toxicity Ablative Regimen;Reduced Intensity Preparative Regimen;Myeloablative Preparative Regimen
19 Alefacept and Allogeneic Hematopoietic Stem Cell Transplantation Terminated NCT01319851 Not Applicable 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:

41
Neutrophil, Bone, Myeloid, Bone Marrow, Liver, Lung, Skin
Sources

Publications for Severe Congenital Neutropenia

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Articles related to Severe Congenital Neutropenia:

(show top 50) (show all 311)
# Title Authors Year
1
How we approach: Severe congenital neutropenia and myelofibrosis due to mutations in VPS45. ( 30294941 )
2019
2
Mechanisms of leukemic transformation in congenital neutropenia. ( 30431463 )
2019
3
Successful second hematopoietic cell transplantation in severe congenital neutropenia. ( 29076228 )
2018
4
Severe Congenital Neutropenia associated with SRP54 mutation in 22q11.2 Deletion Syndrome: Hematopoietic Stem Cell Transplantation Results in Correction of Neutropenia with Adequate Immune Reconstitution. ( 29956078 )
2018
5
Identification of novel <i>MECOM</i> gene fusion and personalized therapeutic targets through integrative clinical sequencing in secondary acute myeloid leukemia in a patient with severe congenital neutropenia: a case report and literature review. ( 29572239 )
2018
6
Mutations in <i>SRP54</i> gene cause severe congenital neutropenia as well as Shwachman-Diamond-like syndrome. ( 29914977 )
2018
7
Pyoderma Gangrenosum Secondary to Severe Congenital Neutropenia. ( 29707446 )
2018
8
Novel Gene Mutation in a Chinese Boy with Severe Congenital Neutropenia. ( 29744746 )
2018
9
Clinical, Laboratory, and Molecular Characteristics and Remission Status in Children With Severe Congenital and Non-congenital Neutropenia. ( 30386760 )
2018
10
Coexistence of Gaucher Disease and severe congenital neutropenia. ( 30473482 )
2018
11
Congenital Neutropenia Patient With Hypomorphic Biallelic CSF3R Mutation Responding to GCSF. ( 30028820 )
2018
12
Both Granulocytic and Non-Granulocytic Blood Cells Are Affected in Patients with Severe Congenital Neutropenia and Their Non-Neutropenic Family Members: An Evaluation of Morphology, Function, and Cell Death ( 30040071 )
2018
13
JAGN1 is required for fungal killing in neutrophil extracellular traps: Implications for severe congenital neutropenia. ( 30106500 )
2018
14
Spectrum of ELANE mutations in congenital neutropenia: a single-centre study in patients of Indian origin. ( 30171085 )
2018
15
A Truncated G-CSFR Inhibits Apoptosis Induced by Neutrophil Elastase G185R Mutant: Implication for Understanding CSF3R Mutations in Severe Congenital Neutropenia. ( 28073911 )
2017
16
A novel homozygous VPS45 p.P468L mutation leading to severe congenital neutropenia with myelofibrosis. ( 28453180 )
2017
17
Granulocyte colony-stimulating factor receptor signaling in severe congenital neutropenia, chronic neutrophilic leukemia, and related malignancies. ( 27789332 )
2017
18
A GCSFR/CSF3R zebrafish mutant models the persistent basal neutrophil deficiency of severe congenital neutropenia. ( 28281657 )
2017
19
Obstructive sleep apnea in a 5 month old with tonsillar hypertrophy secondary to congenital neutropenia: Case report and literature review. ( 28390595 )
2017
20
A Severe Congenital Neutropenia Type 4 Case (G6PC3 Mutation) Presented With Large Platelets in the Peripheral Smear. ( 26808373 )
2016
21
Long-term use of Pegfilgrastim in children with severe congenital neutropenia: clinical and pharmacokinetic data. ( 27621310 )
2016
22
Gangrenous appendicitis in a patient with severe congenital neutropenia. ( 27804250 )
2016
23
Successful non-myeloablative allogenic bone marrow transplantation in a child with severe congenital neutropenia complicated by chronic pulmonary infection. ( 27384854 )
2016
24
Case Reports of Severe Congenital Neutropenia Treated With Unrelated Cord Blood Transplantation With Reduced-intensity Conditioning. ( 26599988 )
2016
25
A novel ELANE gene mutation in a patient with severe congenital neutropenia and intermittent thrombocytopenia. ( 25882539 )
2015
26
Severe congenital neutropenia with neurological impairment due to a homozygous VPS45 p.E238K mutation: A case report suggesting a genotype-phenotype correlation. ( 26358756 )
2015
27
JAGN1 Deficient Severe Congenital Neutropenia: Two Cases from the Same Family. ( 25851723 )
2015
28
Severe congenital neutropenia caused by the ELANE gene mutation in a Vietnamese boy with misdiagnosis of tuberculosis and autoimmune neutropenia: a case report. ( 25705433 )
2015
29
Paternal Somatic Mosaicism of a Novel Frameshift Mutation in ELANE Causing Severe Congenital Neutropenia. ( 26174650 )
2015
30
Functional analysis of mutations in a severe congenital neutropenia syndrome caused by glucose-6-phosphatase-I^ deficiency. ( 25492228 )
2015
31
Lethal sepsis and malignant transformation in severe congenital neutropenia: Report from the Italian Neutropenia Registry. ( 25619745 )
2015
32
Recurrence of Neonatal Lupus Post-Cord Blood Transplant for Severe Congenital Neutropenia. ( 26195545 )
2015
33
Genetic analysis and clinical picture of severe congenital neutropenia in Israel. ( 25284454 )
2015
34
HSCT in severe congenital neutropenia. ( 26472738 )
2015
35
Game of clones: the genomic evolution of severe congenital neutropenia. ( 26637693 )
2015
36
Stem cell transplantation in severe congenital neutropenia: an analysis from the European Society for Blood and Marrow Transplantation. ( 26185129 )
2015
37
Clinical characteristics of severe congenital neutropenia caused by novel ELANE gene mutations. ( 25162927 )
2015
38
Different clinical phenotypes in familial severe congenital neutropenia cases with same mutation of the ELANE gene. ( 24616599 )
2014
39
Inherited biallelic CSF3R mutations in severe congenital neutropenia. ( 24753537 )
2014
40
Sea-blue histiocytes in the bone marrow of a boy with severe congenital neutropenia associated with G6PC3 mutation. ( 24446813 )
2014
41
Severe congenital neutropenia due to G6PC3 deficiency: early and delayed phenotype in two patients with two novel mutations. ( 25391451 )
2014
42
Cooperativity of RUNX1 and CSF3R mutations in severe congenital neutropenia: a unique pathway in myeloid leukemogenesis. ( 24523240 )
2014
43
Successful treatment with allogenic hematopoietic stem cell transplantation of a severe congenital neutropenia patient harboring a novel ELANE mutation. ( 25501410 )
2014
44
Genetic correction of HAX1 in induced pluripotent stem cells from a patient with severe congenital neutropenia improves defective granulopoiesis. ( 23975175 )
2014
45
Severe congenital neutropenia: new lane for ELANE. ( 24458273 )
2014
46
Clinical spectrum and long-term follow-up of 14 cases with G6PC3 mutations from the French Severe Congenital Neutropenia Registry. ( 25491320 )
2014
47
Allogeneic stem cell transplantation for patients with acute myeloid leukaemia developing from severe congenital neutropenia. ( 24422727 )
2014
48
Severe congenital neutropenia with a novel ELANE mutation in 2 Mexican patients. ( 25219109 )
2014
49
A novel G6PC3 gene mutation in severe congenital neutropenia: pancytopenia and variable bone marrow phenotype can also be part of this syndrome. ( 24750412 )
2014
50
Crusted scabies in a 15-year-old boy with congenital neutropenia and myelodysplastic syndrome. ( 24470010 )
2014
Sources

Variations for Severe Congenital Neutropenia

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ClinVar genetic disease variations for Severe Congenital Neutropenia:

6 (show top 50) (show all 186)
# Gene Variation Type Significance SNP ID Assembly Location
1 TCIRG1 NM_006019.3(TCIRG1): c.2206C> A (p.Arg736Ser) single nucleotide variant Conflicting interpretations of pathogenicity rs587779413 GRCh37 Chromosome 11, 67817691: 67817691
2 TCIRG1 NM_006019.3(TCIRG1): c.2206C> A (p.Arg736Ser) single nucleotide variant Conflicting interpretations of pathogenicity rs587779413 GRCh38 Chromosome 11, 68050224: 68050224
3 JAGN1 NM_032492.3(JAGN1): c.3G> A (p.Met1Ile) single nucleotide variant Pathogenic rs587777727 GRCh38 Chromosome 3, 9890725: 9890725
4 JAGN1 NM_032492.3(JAGN1): c.3G> A (p.Met1Ile) single nucleotide variant Pathogenic rs587777727 GRCh37 Chromosome 3, 9932409: 9932409
5 JAGN1 NM_032492.3(JAGN1): c.130C> T (p.His44Tyr) single nucleotide variant Pathogenic rs587777728 GRCh37 Chromosome 3, 9934639: 9934639
6 JAGN1 NM_032492.3(JAGN1): c.130C> T (p.His44Tyr) single nucleotide variant Pathogenic rs587777728 GRCh38 Chromosome 3, 9892955: 9892955
7 JAGN1 NM_032492.3(JAGN1): c.63G> T (p.Glu21Asp) single nucleotide variant Pathogenic rs587777729 GRCh38 Chromosome 3, 9890785: 9890785
8 JAGN1 NM_032492.3(JAGN1): c.63G> T (p.Glu21Asp) single nucleotide variant Pathogenic rs587777729 GRCh37 Chromosome 3, 9932469: 9932469
9 JAGN1 NM_032492.3(JAGN1): c.485A> G (p.Gln162Arg) single nucleotide variant Pathogenic rs587777730 GRCh38 Chromosome 3, 9893310: 9893310
10 JAGN1 NM_032492.3(JAGN1): c.485A> G (p.Gln162Arg) single nucleotide variant Pathogenic rs587777730 GRCh37 Chromosome 3, 9934994: 9934994
11 JAGN1 NM_032492.3(JAGN1): c.35_43delCCGACGGCA (p.Thr12_Gly14del) deletion Pathogenic rs587777731 GRCh38 Chromosome 3, 9890757: 9890765
12 JAGN1 NM_032492.3(JAGN1): c.35_43delCCGACGGCA (p.Thr12_Gly14del) deletion Pathogenic rs587777731 GRCh37 Chromosome 3, 9932441: 9932449
13 CSF3R NM_000760.3(CSF3R): c.922C> T (p.Arg308Cys) single nucleotide variant Pathogenic rs606231473 GRCh38 Chromosome 1, 36472313: 36472313
14 CSF3R NM_000760.3(CSF3R): c.922C> T (p.Arg308Cys) single nucleotide variant Pathogenic rs606231473 GRCh37 Chromosome 1, 36937914: 36937914
15 JAGN1 NM_032492.3(JAGN1): c.40G> A (p.Gly14Ser) single nucleotide variant Pathogenic rs786205704 GRCh37 Chromosome 3, 9932446: 9932446
16 JAGN1 NM_032492.3(JAGN1): c.40G> A (p.Gly14Ser) single nucleotide variant Pathogenic rs786205704 GRCh38 Chromosome 3, 9890762: 9890762
17 JAGN1 NM_032492.3(JAGN1): c.59G> A (p.Arg20Gln) single nucleotide variant Pathogenic rs777966677 GRCh37 Chromosome 3, 9932465: 9932465
18 JAGN1 NM_032492.3(JAGN1): c.59G> A (p.Arg20Gln) single nucleotide variant Pathogenic rs777966677 GRCh38 Chromosome 3, 9890781: 9890781
19 JAGN1 NM_032492.3(JAGN1): c.297C> G (p.Tyr99Ter) single nucleotide variant Pathogenic rs786205705 GRCh37 Chromosome 3, 9934806: 9934806
20 JAGN1 NM_032492.3(JAGN1): c.297C> G (p.Tyr99Ter) single nucleotide variant Pathogenic rs786205705 GRCh38 Chromosome 3, 9893122: 9893122
21 GFI1 NM_005263.3(GFI1): c.465C> T (p.Cys155=) single nucleotide variant Benign rs11164605 GRCh37 Chromosome 1, 92946479: 92946479
22 GFI1 NM_005263.3(GFI1): c.465C> T (p.Cys155=) single nucleotide variant Benign rs11164605 GRCh38 Chromosome 1, 92480922: 92480922
23 G6PC3 NM_138387.3(G6PC3): c.*2T> C single nucleotide variant Conflicting interpretations of pathogenicity rs113416399 GRCh37 Chromosome 17, 42153413: 42153413
24 G6PC3 NM_138387.3(G6PC3): c.*2T> C single nucleotide variant Conflicting interpretations of pathogenicity rs113416399 GRCh38 Chromosome 17, 44076045: 44076045
25 HAX1 NM_006118.3(HAX1): c.53+14C> T single nucleotide variant Likely benign rs115683875 GRCh37 Chromosome 1, 154245266: 154245266
26 HAX1 NM_006118.3(HAX1): c.53+14C> T single nucleotide variant Likely benign rs115683875 GRCh38 Chromosome 1, 154272790: 154272790
27 HAX1 NM_006118.3(HAX1): c.159T> C (p.Ser53=) single nucleotide variant Benign/Likely benign rs13796 GRCh37 Chromosome 1, 154245917: 154245917
28 HAX1 NM_006118.3(HAX1): c.159T> C (p.Ser53=) single nucleotide variant Benign/Likely benign rs13796 GRCh38 Chromosome 1, 154273441: 154273441
29 GFI1 NM_005263.3(GFI1): c.1047C> T (p.Phe349=) single nucleotide variant Benign/Likely benign rs80337126 GRCh38 Chromosome 1, 92478631: 92478631
30 GFI1 NM_005263.3(GFI1): c.1047C> T (p.Phe349=) single nucleotide variant Benign/Likely benign rs80337126 GRCh37 Chromosome 1, 92944188: 92944188
31 GFI1 NM_005263.3(GFI1): c.648A> G (p.Ala216=) single nucleotide variant Benign rs114464352 GRCh38 Chromosome 1, 92480739: 92480739
32 GFI1 NM_005263.3(GFI1): c.648A> G (p.Ala216=) single nucleotide variant Benign rs114464352 GRCh37 Chromosome 1, 92946296: 92946296
33 GFI1 NM_005263.3(GFI1): c.319C> G (p.Pro107Ala) single nucleotide variant Likely benign rs149914857 GRCh38 Chromosome 1, 92481068: 92481068
34 GFI1 NM_005263.3(GFI1): c.319C> G (p.Pro107Ala) single nucleotide variant Likely benign rs149914857 GRCh37 Chromosome 1, 92946625: 92946625
35 GFI1 NM_005263.3(GFI1): c.168C> T (p.Ser56=) single nucleotide variant Benign/Likely benign rs143913803 GRCh37 Chromosome 1, 92948551: 92948551
36 GFI1 NM_005263.3(GFI1): c.168C> T (p.Ser56=) single nucleotide variant Benign/Likely benign rs143913803 GRCh38 Chromosome 1, 92482994: 92482994
37 GFI1 NM_005263.3(GFI1): c.107G> A (p.Ser36Asn) single nucleotide variant Benign rs34631763 GRCh38 Chromosome 1, 92483381: 92483381
38 GFI1 NM_005263.3(GFI1): c.107G> A (p.Ser36Asn) single nucleotide variant Benign rs34631763 GRCh37 Chromosome 1, 92948938: 92948938
39 G6PC3 NM_138387.3(G6PC3): c.381G> A (p.Thr127=) single nucleotide variant Benign rs3815076 GRCh37 Chromosome 17, 42152103: 42152103
40 G6PC3 NM_138387.3(G6PC3): c.381G> A (p.Thr127=) single nucleotide variant Benign rs3815076 GRCh38 Chromosome 17, 44074735: 44074735
41 HAX1 NM_006118.3(HAX1): c.-53delC deletion Likely benign rs886045319 GRCh38 Chromosome 1, 154272671: 154272671
42 HAX1 NM_006118.3(HAX1): c.-53delC deletion Likely benign rs886045319 GRCh37 Chromosome 1, 154245147: 154245147
43 HAX1 NM_006118.3(HAX1): c.137G> C (p.Arg46Pro) single nucleotide variant Uncertain significance rs761500862 GRCh38 Chromosome 1, 154273419: 154273419
44 HAX1 NM_006118.3(HAX1): c.137G> C (p.Arg46Pro) single nucleotide variant Uncertain significance rs761500862 GRCh37 Chromosome 1, 154245895: 154245895
45 HAX1 NM_006118.3(HAX1): c.593C> T (p.Pro198Leu) single nucleotide variant Uncertain significance rs146152769 GRCh38 Chromosome 1, 154275190: 154275190
46 HAX1 NM_006118.3(HAX1): c.593C> T (p.Pro198Leu) single nucleotide variant Uncertain significance rs146152769 GRCh37 Chromosome 1, 154247666: 154247666
47 HAX1 NM_006118.3(HAX1): c.*1C> G single nucleotide variant Uncertain significance rs747961567 GRCh38 Chromosome 1, 154275702: 154275702
48 HAX1 NM_006118.3(HAX1): c.*1C> G single nucleotide variant Uncertain significance rs747961567 GRCh37 Chromosome 1, 154248178: 154248178
49 HAX1 NM_006118.3(HAX1): c.-52G> T single nucleotide variant Likely benign rs578086387 GRCh38 Chromosome 1, 154272672: 154272672
50 HAX1 NM_006118.3(HAX1): c.-52G> T single nucleotide variant Likely benign rs578086387 GRCh37 Chromosome 1, 154245148: 154245148
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 21)
# Super pathways Score Top Affiliating Genes
1
Innate Immune System 66
Show member pathways
 13.85 BIRC5 CSF2 CSF3 CSF3R ELANE IL3
2
Akt Signaling 64
Show member pathways
 13.22 CSF2 CSF3 CSF3R IL3 JAK2 KITLG
3
Cytokine Signaling in Immune system 66
Show member pathways
 13.08 BIRC5 CSF2 CSF3 CSF3R IL3 JAK2
4
PAK Pathway 64
Show member pathways
 12.99 CSF2 CSF3 CSF3R IL3 JAK2 KITLG
5
PI3K-Akt signaling pathway 37
Show member pathways
 12.77 CSF3 CSF3R G6PC3 IL3 JAK2 KITLG
6
Pathways in cancer 37
12.67 BIRC5 CSF3R IL3 JAK2 KITLG
7
Immune response Role of DAP12 receptors in NK cells 22
Show member pathways
 12.35 CSF2 IL3 PTPN11 WAS
8
Kit receptor signaling pathway 1
Show member pathways
 12 IL3 JAK2 KITLG PTPN11
9
JAK-STAT signaling pathway (KEGG) 37
Show member pathways
 12 CSF2 CSF3 CSF3R IL3 JAK2 PTPN11
10
G beta-gamma signalling through PI3Kgamma 66
Show member pathways
 11.96 CSF2 IL3 JAK2 PTPN11
11
Immune response IFN gamma signaling pathway 22
Show member pathways
 11.9 IL3 JAK2 KITLG PTPN11
12
Immune response IL-2 activation and signaling pathway 22
Show member pathways
 11.79 IL3 JAK2 PTPN11
13
Cytokine production by Th17 cells in CF (Mouse model) 22
Show member pathways
 11.71 CSF2 CSF3 JAK2
14
Jak-Stat Signaling Pathway (sino) 67
11.68 CSF3R IL3 JAK2 PTPN11
15
Adipocytokine signaling pathway 37
11.55 G6PC3 JAK2 PTPN11
16
Hematopoietic Stem Cell Differentiation Pathways and Lineage-specific Markers 65
11.42 CSF2 CSF3 CSF3R IL3 KITLG
17
Interleukin-11 Signaling Pathway 1
11.33 BIRC5 JAK2 PTPN11
18
Hematopoietic Stem Cell Differentiation 1
11.24 CSF2 CSF3 IL3 KITLG
19
Development_Leptin signaling via JAK/STAT and MAPK cascades 22
Show member pathways
 11.08 JAK2 PTPN11
20
Cytokines and Inflammatory Response 1
11.04 CSF2 CSF3 IL3
21
Hematopoietic cell lineage 37
11.01 CSF2 CSF3 CSF3R IL3 KITLG
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 18)
# Name GO ID Score Top Affiliating Genes
1 regulation of signaling receptor activity GO:0010469 9.84 CSF2 CSF3 IL3 KITLG
2 peptidyl-tyrosine phosphorylation GO:0018108 9.73 CSF2 IL3 JAK2
3 cellular response to lipopolysaccharide GO:0071222 9.72 CSF2 CSF3 GFI1
4 MAPK cascade GO:0000165 9.71 CSF2 IL3 JAK2 KITLG
5 positive regulation of phosphatidylinositol 3-kinase signaling GO:0014068 9.63 CSF3 HAX1 JAK2
6 positive regulation of cell proliferation GO:0008284 9.63 BIRC5 CSF2 CSF3 IL3 JAK2 KITLG
7 positive regulation of tyrosine phosphorylation of STAT protein GO:0042531 9.61 CSF2 IL3 JAK2
8 platelet-derived growth factor receptor signaling pathway GO:0048008 9.58 JAK2 PTPN11
9 defense response to fungus GO:0050832 9.57 ELANE JAGN1
10 positive regulation of protein kinase B signaling GO:0051897 9.56 CSF3 HAX1 KITLG PTPN11
11 cellular response to cytokine stimulus GO:0071345 9.54 CSF3 HAX1 PTPN11
12 positive regulation of actin cytoskeleton reorganization GO:2000251 9.52 CSF3 HAX1
13 embryonic hemopoiesis GO:0035162 9.51 IL3 KITLG
14 interleukin-6-mediated signaling pathway GO:0070102 9.49 JAK2 PTPN11
15 regulation of myeloid cell differentiation GO:0045637 9.48 CSF2 CSF3R
16 positive regulation of peptidyl-tyrosine phosphorylation GO:0050731 9.35 CSF3 HAX1 IL3 JAK2 KITLG
17 neutrophil differentiation GO:0030223 9.32 CSF2 JAGN1
18 cytokine-mediated signaling pathway GO:0019221 9.17 BIRC5 CSF2 CSF3 CSF3R IL3 JAK2

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

# Name GO ID Score Top Affiliating Genes
1 protein tyrosine kinase activity GO:0004713 9.58 CSF2 IL3 JAK2
2 cytokine activity GO:0005125 9.46 CSF2 CSF3 IL3 KITLG
3 phospholipase binding GO:0043274 9.37 PTPN11 WAS
4 insulin receptor substrate binding GO:0043560 9.32 JAK2 PTPN11
5 peptide hormone receptor binding GO:0051428 9.26 JAK2 PTPN11
6 growth factor activity GO:0008083 9.26 CSF2 CSF3 IL3 KITLG
7 Ras guanyl-nucleotide exchange factor activity GO:0005088 8.92 CSF2 IL3 JAK2 KITLG
Sources

Sources for Severe Congenital Neutropenia

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3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 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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