MCID: IMM078
MIFTS: 38

Immunodeficiency 21

Categories: Genetic diseases, Rare diseases, Infectious diseases, Immune diseases, Blood diseases

Aliases & Classifications for Immunodeficiency 21

MalaCards integrated aliases for Immunodeficiency 21:

Name: Immunodeficiency 21 53 71 69
Dendritic Cell, Monocyte, B Lymphocyte, and Natural Killer Lymphocyte Deficiency 53 49 28 13
Monocytopenia and Mycobacterial Infection Syndrome 53 49 55 71
Monomac 53 49 55 71
Dcml 53 49 71
Monocytopenia with Susceptibility to Mycobacterial, Fungal, and Papillomavirus Infections and Myelodysplasia 53 49
Combined Immunodeficiency with Susceptibility to Mycobacterial, Viral, and Fungal Infections 53 49
Monocytopenia with Susceptibility to Infections 49 55
Gata2 Deficiency 53 49
Imd21 53 71
Monocytopenia with Susceptibility to Mycobacterial Fungal and Papillomavirus Infections and Myelodysplasia 71
Combined Immunodeficiency with Susceptibility to Mycobacterial, Viral and Fungal Infections 55
Monocytopenia with Mycobacterial, Fungal, and Papillomavirus Infections and Myelodysplasia 53
Combined Immunodeficiency with Susceptibility to Mycobacterial Viral and Fungal Infections 71
Dendritic Cell, Monocyte, B Lymphocyte, and Natural Killer Lymphocyte Deficiency; Dcml 53
Dendritic Cell Monocyte Lymphocyte B and Natural Killer Lymphocyte Deficiency 71
Combined Immunodeficiency with Mycobacterial, Viral, and Fungal Infections 53
Monocyte-B-Natural Killer-Dendritic Cell Deficiency Syndrome 55
Monocytopenia and Mycobacterial Infection Syndrome; Monomac 53
Monocyte - B - Natural Killer - Dendritic Cell Deficiency 49
Dendritic Cell, Monocyte, B and Nk Lymphoid Deficiency 55

Characteristics:

Orphanet epidemiological data:

55
monocytopenia with susceptibility to infections
Inheritance: Autosomal dominant,Not applicable; Prevalence: <1/1000000 (Worldwide); Age of onset: Adult;

OMIM:

53
Inheritance:
autosomal dominant

Miscellaneous:
variable phenotype
variable age at onset
increased risk of miscarriage


HPO:

31
immunodeficiency 21:
Onset and clinical course phenotypic variability
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 55  
Rare immunological diseases


External Ids:

OMIM 53 614172
Orphanet 55 ORPHA228423
ICD10 via Orphanet 33 D72.8
MedGen 39 C3280030
MeSH 41 D008231
UMLS 69 C3280030

Summaries for Immunodeficiency 21

OMIM : 53 This primary immunodeficiency, designated IMD21, DCML, or MONOMAC, is characterized by profoundly decreased or absent monocytes, B lymphocytes, natural killer (NK) lymphocytes, and circulating and tissue dendritic cells (DCs), with little or no effect on T-cell numbers. Clinical features of IMD21 are variable and include susceptibility to disseminated nontuberculous mycobacterial infections, papillomavirus infections, opportunistic fungal infections, and pulmonary alveolar proteinosis. Bone marrow hypocellularity and dysplasia of myeloid, erythroid, and megakaryocytic lineages are present in most patients, as are karyotypic abnormalities, including monosomy 7 and trisomy 8. In the absence of cytogenetic abnormalities or overt dysplasia, hypoplastic bone marrow may initially be diagnosed as aplastic anemia. Bone marrow transplantation is the only cure. Some patients may have an increased risk of miscarriage. Both autosomal dominant transmission and sporadic cases occur. Less common manifestations of GATA2 deficiency include lymphedema and sensorineural hearing loss, a phenotype usually termed 'Emberger syndrome' (614038) (summary by Bigley et al. (2011), Hsu et al. (2011), and Spinner et al. (2014)). (614172)

MalaCards based summary : Immunodeficiency 21, also known as dendritic cell, monocyte, b lymphocyte, and natural killer lymphocyte deficiency, is related to hematopoietic stem cell transplantation and fibrosis of extraocular muscles, congenital, 1, and has symptoms including immunodeficiency, aplastic anemia and neutropenia. An important gene associated with Immunodeficiency 21 is GATA2 (GATA Binding Protein 2). The drugs Cyclophosphamide and Fludarabine have been mentioned in the context of this disorder. Affiliated tissues include monocytes, myeloid and bone.

NIH Rare Diseases : 49 This condition doesn't have a summary yet. Please see our page(s) on Mendelian susceptibility to mycobacterial diseases and GATA2 deficiency.

UniProtKB/Swiss-Prot : 71 Immunodeficiency 21: An immunodeficiency disease characterized by profoundly decreased or absent monocytes, B-lymphocytes, natural killer lymphocytes, and circulating and tissue dendritic cells, with little or no effect on T- cell numbers. Clinical features of DCML include susceptibility to disseminated non-tuberculous mycobacterial infections, papillomavirus infections, opportunistic fungal infections, and pulmonary alveolar proteinosis. Bone marrow hypocellularity and dysplasia of myeloid, erythroid, and megakaryocytic lineages are present in most patients, as are karyotypic abnormalities, including monosomy 7 and trisomy 8. This syndrome links susceptibility to mycobacterial, viral, and fungal infections with malignancy and can be transmitted in an autosomal dominant pattern.

Related Diseases for Immunodeficiency 21

Diseases related to Immunodeficiency 21 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 11)
# Related Disease Score Top Affiliating Genes
1 hematopoietic stem cell transplantation 10.0
2 fibrosis of extraocular muscles, congenital, 1 10.0
3 pulmonary alveolar proteinosis 10.0
4 lymphedema 10.0
5 pulmonary hypertension 9.9
6 leukemia, acute myeloid 9.9
7 leukemia 9.9
8 myeloid leukemia 9.9
9 aplastic anemia 9.7
10 hemophagocytic lymphohistiocytosis 9.7
11 herpes simplex 9.7

Graphical network of the top 20 diseases related to Immunodeficiency 21:



Diseases related to Immunodeficiency 21

Symptoms & Phenotypes for Immunodeficiency 21

Symptoms via clinical synopsis from OMIM:

53
Immunology:
neutropenia
monocytopenia
primary immunodeficiency
recurrent infections, particularly to viruses and fungi
mycobacterial infections
more
Hematology:
aplastic anemia (in some patients)

RespiratoryLung:
pulmonary alveolar proteinosis (in some patients)

Neoplasia:
susceptibility to myelodysplasia
susceptibility to myeloid leukemia


Clinical features from OMIM:

614172

Human phenotypes related to Immunodeficiency 21:

31 (show all 8)
# Description HPO Frequency HPO Source Accession
1 immunodeficiency 31 HP:0002721
2 aplastic anemia 31 occasional (7.5%) HP:0001915
3 neutropenia 31 HP:0001875
4 recurrent viral infections 31 HP:0004429
5 recurrent fungal infections 31 HP:0002841
6 monocytopenia 31 HP:0012312
7 recurrent mycobacterium avium complex infections 31 HP:0011275
8 abnormal natural killer cell morphology 31 HP:0012176

Drugs & Therapeutics for Immunodeficiency 21

Drugs for Immunodeficiency 21 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 13)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Cyclophosphamide Approved, Investigational Phase 2 50-18-0, 6055-19-2 2907
2
Fludarabine Approved Phase 2 21679-14-1, 75607-67-9 30751
3
Busulfan Approved, Investigational Phase 2 55-98-1 2478
4 Alkylating Agents Phase 2
5 Antilymphocyte Serum Phase 2
6 Antimetabolites Phase 2
7 Antimetabolites, Antineoplastic Phase 2
8 Antirheumatic Agents Phase 2
9 Immunosuppressive Agents Phase 2
10 Antibodies
11 Autoantibodies
12 Immunoglobulins
13 Yellow Dock Nutraceutical

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Pilot and Feasibility Study of Reduced-Intensity Hematopoietic Stem Cell Transplant for MonoMAC Completed NCT00923364 Phase 2 Cyclophosphamide (CTX, Cytoxan);Fludarabine(Fludara,Berlex Laboratories);Equine Anti-Thymocyte Globulin
2 Allogeneic Hematopoietic Stem Cell Transplant for GATA2 Mutations Recruiting NCT01861106 Phase 2 Busulfan Test dose;Fludarabine(Fludara, Berlex Laboratories);Busulfan (Busulfex);Cyclophosphamide(CTX, Cytoxan);Equine Anti-Thymocyte Globulin
3 Natural History Study of GATA2 Deficiency and Related Disorders Recruiting NCT01905826
4 Apheresis of Patients With Immunodeficiency Recruiting NCT01212055
5 Detection and Characterization of Infections and Infection Susceptibility Recruiting NCT00404560

Search NIH Clinical Center for Immunodeficiency 21

Genetic Tests for Immunodeficiency 21

Genetic tests related to Immunodeficiency 21:

# Genetic test Affiliating Genes
1 Dendritic Cell, Monocyte, B Lymphocyte, and Natural Killer Lymphocyte Deficiency 28 GATA2

Anatomical Context for Immunodeficiency 21

MalaCards organs/tissues related to Immunodeficiency 21:

38
Monocytes, Myeloid, Bone, Bone Marrow, T Cells, Nk Cells, B Cells

Publications for Immunodeficiency 21

Articles related to Immunodeficiency 21:

(show all 24)
# Title Authors Year
1
Allogeneic Hematopoietic Stem-Cell Transplantation for GATA2 Deficiency Using a Busulfan-Based Regimen. ( 29412158 )
2018
2
Haemodynamically proven pulmonary hypertension in a patient with GATA2 deficiency-associated pulmonary alveolarA proteinosis and fibrosis. ( 28495697 )
2017
3
Resolution of Multifocal Epstein-Barr Virus-Related Smooth Muscle Tumor in a Patient with GATA2 Deficiency Following Hematopoietic Stem Cell Transplantation. ( 27924436 )
2017
4
Vulvar lymphedema and refractory VIN-III heralding GATA2 deficiency syndrome. ( 28947108 )
2017
5
Haemodynamically proven pulmonary hypertension in a patient with GATA2 deficiency-associated pulmonary alveolar proteinosis and fibrosis. ( 28495695 )
2017
6
Successful Myeloablative Matched Unrelated Donor Hematopoietic Stem Cell Transplantation in a Young Girl With GATA2 Deficiency and Emberger Syndrome. ( 28234738 )
2017
7
Association of pulmonary alveolar proteinosis and fibrosis: patient with GATA2 deficiency. ( 27799394 )
2016
8
Mediastinal and Disseminated Mycobacterium kansasii Disease in GATA2 Deficiency. ( 27607353 )
2016
9
Association of GATA2 Deficiency With Severe Primary Epstein-Barr Virus (EBV) Infection and EBV-associated Cancers. ( 27169477 )
2016
10
GATA2 deficiency underlying severe blastomycosis and fatal herpes simplex virus-associated hemophagocytic lymphohistiocytosis. ( 26395816 )
2015
11
GATA2 deficiency in children and adults with severe pulmonary alveolar proteinosis and hematologic disorders. ( 26264606 )
2015
12
GATA2 deficiency: a protean disorder of hematopoiesis, lymphatics, and immunity. ( 24227816 )
2014
13
[GATA2 deficiency]. ( 25509816 )
2014
14
GATA2 deficiency-associated bone marrow disorder differs from idiopathic aplastic anemia. ( 25359990 )
2014
15
[MonoMAC syndrome]. ( 25140787 )
2014
16
High frequency of GATA2 mutations in patients with mild chronic neutropenia evolving to MonoMac syndrome, myelodysplasia, and acute myeloid leukemia. ( 23223431 )
2013
17
Mass spectrometry-based proteomics identifies UPF1 as a critical gene expression regulator in MonoMac 6 cells. ( 23642263 )
2013
18
GATA2 haploinsufficiency caused by mutations in a conserved intronic element leads to MonoMAC syndrome. ( 23502222 )
2013
19
Loss-of-function germline GATA2 mutations in patients with MDS/AML or MonoMAC syndrome and primary lymphedema reveal a key role for GATA2 in the lymphatic vasculature. ( 22147895 )
2012
20
Mutations in GATA2 are associated with the autosomal dominant and sporadic monocytopenia and mycobacterial infection (MonoMAC) syndrome. ( 21670465 )
2011
21
Successful allogeneic hematopoietic stem cell transplantation for GATA2 deficiency. ( 21816832 )
2011
22
Arachidonic acid increases matrix metalloproteinase 9 secretion and expression in human monocytic MonoMac 6 cells. ( 19331685 )
2009
23
OxLDL immune complexes activate complement and induce cytokine production by MonoMac 6 cells and human macrophages. ( 16804192 )
2006
24
Binding of Amadori glucose-modified albumin by the monocytic cell line MonoMac 6 activates protein kinase C epsilon protein tyrosine kinases and the transcription factors AP-1 and NF-kappaB. ( 12441666 )
2001

Variations for Immunodeficiency 21

UniProtKB/Swiss-Prot genetic disease variations for Immunodeficiency 21:

71
# Symbol AA change Variation ID SNP ID
1 GATA2 p.Pro254Leu VAR_066405 rs387906630
2 GATA2 p.Thr354Met VAR_066406 rs387906631
3 GATA2 p.Arg398Trp VAR_066407 rs387906629

ClinVar genetic disease variations for Immunodeficiency 21:

6 (show all 13)
# Gene Variation Type Significance SNP ID Assembly Location
1 GATA2 NM_032638.4(GATA2): c.1192C> T (p.Arg398Trp) single nucleotide variant Pathogenic/Likely pathogenic rs387906629 GRCh37 Chromosome 3, 128200113: 128200113
2 GATA2 NM_001145661.1(GATA2): c.761C> T (p.Pro254Leu) single nucleotide variant Pathogenic rs387906630 GRCh37 Chromosome 3, 128204680: 128204680
3 GATA2 NM_001145661.1(GATA2): c.1061C> T (p.Thr354Met) single nucleotide variant Pathogenic/Likely pathogenic,risk factor rs387906631 GRCh37 Chromosome 3, 128200744: 128200744
4 GATA2 NM_001145661.1(GATA2): c.-200_871+527del2032 deletion Pathogenic GRCh38 Chromosome 3, 128485200: 128487231
5 GATA2 NM_001145661.1(GATA2): c.1084_1095delCGAAACGCCAAC (p.Arg362_Asn365del) deletion Pathogenic rs869320734 GRCh37 Chromosome 3, 128200710: 128200721
6 GATA2 NM_001145661.1(GATA2): c.243delAinsGC (p.Gly82Argfs) indel Pathogenic rs869320735 GRCh37 Chromosome 3, 128205198: 128205198
7 GATA2 NM_032638.4(GATA2): c.599dupG (p.Ser201Terfs) duplication Pathogenic rs768767517 GRCh37 Chromosome 3, 128204842: 128204842
8 GATA2 NM_001145661.1(GATA2): c.1018-1G> T single nucleotide variant Pathogenic rs869320668 GRCh37 Chromosome 3, 128200788: 128200788
9 GATA2 NM_001145661.1(GATA2): c.1017+513_1017+540del28 deletion Pathogenic GRCh37 Chromosome 3, 128202163: 128202190
10 GATA2 NM_032638.4(GATA2): c.1113C> A (p.Asn371Lys) single nucleotide variant Likely pathogenic rs376003468 GRCh38 Chromosome 3, 128481849: 128481849
11 GATA2 NM_001145661.1(GATA2): c.1021_1024dupGCCG (p.Ala342Glyfs) duplication Pathogenic rs869320770 GRCh38 Chromosome 3, 128481938: 128481941
12 GATA2 NM_032638.4(GATA2): c.1187G> A (p.Arg396Gln) single nucleotide variant Pathogenic GRCh38 Chromosome 3, 128481275: 128481275
13 GATA2 NM_032638.4(GATA2): c.1081C> T (p.Arg361Cys) single nucleotide variant Likely pathogenic GRCh38 Chromosome 3, 128481881: 128481881

Expression for Immunodeficiency 21

Search GEO for disease gene expression data for Immunodeficiency 21.

Pathways for Immunodeficiency 21

GO Terms for Immunodeficiency 21

Sources for Immunodeficiency 21

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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