IMD21
MCID: IMM078
MIFTS: 39

Immunodeficiency 21 (IMD21)

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

Aliases & Classifications for Immunodeficiency 21

MalaCards integrated aliases for Immunodeficiency 21:

Name: Immunodeficiency 21 57 75 73
Dendritic Cell, Monocyte, B Lymphocyte, and Natural Killer Lymphocyte Deficiency 57 53 29 13 6 40
Monocytopenia and Mycobacterial Infection Syndrome 57 53 59 75
Monomac 57 53 59 75
Dcml 57 53 75
Monocytopenia with Susceptibility to Mycobacterial, Fungal, and Papillomavirus Infections and Myelodysplasia 57 53
Combined Immunodeficiency with Susceptibility to Mycobacterial, Viral, and Fungal Infections 57 53
Monocytopenia with Susceptibility to Infections 53 59
Gata2 Deficiency 57 53
Imd21 57 75
Monocytopenia with Susceptibility to Mycobacterial Fungal and Papillomavirus Infections and Myelodysplasia 75
Combined Immunodeficiency with Susceptibility to Mycobacterial, Viral and Fungal Infections 59
Monocytopenia with Mycobacterial, Fungal, and Papillomavirus Infections and Myelodysplasia 57
Combined Immunodeficiency with Susceptibility to Mycobacterial Viral and Fungal Infections 75
Dendritic Cell, Monocyte, B Lymphocyte, and Natural Killer Lymphocyte Deficiency; Dcml 57
Dendritic Cell Monocyte Lymphocyte B and Natural Killer Lymphocyte Deficiency 75
Combined Immunodeficiency with Mycobacterial, Viral, and Fungal Infections 57
Monocyte-B-Natural Killer-Dendritic Cell Deficiency Syndrome 59
Monocytopenia and Mycobacterial Infection Syndrome; Monomac 57
Monocyte - B - Natural Killer - Dendritic Cell Deficiency 53
Dendritic Cell, Monocyte, B and Nk Lymphoid Deficiency 59

Characteristics:

Orphanet epidemiological data:

59
monocytopenia with susceptibility to infections
Inheritance: Autosomal dominant,Not applicable; Prevalence: <1/1000000 (Worldwide); Age of onset: Adult;

OMIM:

57
Inheritance:
autosomal dominant

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


HPO:

32
immunodeficiency 21:
Onset and clinical course phenotypic variability
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 59  
Rare immunological diseases


Summaries for Immunodeficiency 21

OMIM : 57 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 lymphedema and pulmonary alveolar proteinosis. An important gene associated with Immunodeficiency 21 is GATA2 (GATA Binding Protein 2). The drugs Fludarabine and Cyclophosphamide have been mentioned in the context of this disorder. Affiliated tissues include monocytes, myeloid and bone, and related phenotypes are immunodeficiency and aplastic anemia

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 228423Disease definitionMonocytopenia with susceptibility to infections is a rare, genetic, primary immunodeficiency disorder characterized by profound circulating monocytopenia, B- and NK-cell lymphopenia and severe dentritic cell decrease, which manifests clinically with disseminated mycobacterial and viral infections, as well as opportunistic fungal and parasitic infections and frequent pulmonary alveolar proteinosis. Predisposition to developping myeloid neoplasms is associated.Visit the Orphanet disease page for more resources.

UniProtKB/Swiss-Prot : 75 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

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:

57
Immunology:
neutropenia
monocytopenia
primary immunodeficiency
recurrent infections, particularly to viruses and fungi
mycobacterial infections
more
Hematology:
aplastic anemia (in some patients)

Respiratory Lung:
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:

32 (show all 11)
# Description HPO Frequency HPO Source Accession
1 immunodeficiency 32 HP:0002721
2 aplastic anemia 32 occasional (7.5%) HP:0001915
3 myelodysplasia 32 HP:0002863
4 lymphopenia 32 HP:0001888
5 neutropenia 32 HP:0001875
6 recurrent viral infections 32 HP:0004429
7 recurrent fungal infections 32 HP:0002841
8 myeloid leukemia 32 HP:0012324
9 monocytopenia 32 HP:0012312
10 recurrent mycobacterium avium complex infections 32 HP:0011275
11 abnormal natural killer cell morphology 32 HP:0012176

Drugs & Therapeutics for Immunodeficiency 21

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

(show all 15)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Fludarabine Approved Phase 2 75607-67-9, 21679-14-1 30751
2
Cyclophosphamide Approved, Investigational Phase 2 6055-19-2, 50-18-0 2907
3
Busulfan Approved, Investigational Phase 2 55-98-1 2478
4 Antineoplastic Agents, Alkylating Phase 2
5 Immunologic Factors Phase 2
6 Alkylating Agents Phase 2
7 Antirheumatic Agents Phase 2
8 Antimetabolites Phase 2
9 Antilymphocyte Serum Phase 2
10 Immunosuppressive Agents Phase 2
11 Antimetabolites, Antineoplastic Phase 2
12 Yellow Dock
13 Immunoglobulins
14 Autoantibodies
15 Antibodies

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)
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 29 GATA2

Anatomical Context for Immunodeficiency 21

MalaCards organs/tissues related to Immunodeficiency 21:

41
Monocytes, Myeloid, Bone, Bone Marrow, T Cells, Nk Cells, Dentritic 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
Folliculotropic mycosis fungoides associated with GATA2 deficiency: a new skin manifestation. ( 30101490 )
2018
3
Vulvar Cancer as a Result of GATA2 Deficiency, a Rare Genetic Immunodeficiency Syndrome. ( 30303925 )
2018
4
Oocyte cryopreservation for women with GATA2 deficiency. ( 29532200 )
2018
5
Haemodynamically proven pulmonary hypertension in a patient with GATA2 deficiency-associated pulmonary alveolarA proteinosis and fibrosis. ( 28495697 )
2017
6
Resolution of Multifocal Epstein-Barr Virus-Related Smooth Muscle Tumor in a Patient with GATA2 Deficiency Following Hematopoietic Stem Cell Transplantation. ( 27924436 )
2017
7
Successful Myeloablative Matched Unrelated Donor Hematopoietic Stem Cell Transplantation in a Young Girl With GATA2 Deficiency and Emberger Syndrome. ( 28234738 )
2017
8
Vulvar lymphedema and refractory VIN-III heralding GATA2 deficiency syndrome. ( 28947108 )
2017
9
Haemodynamically proven pulmonary hypertension in a patient with GATA2 deficiency-associated pulmonary alveolar proteinosis and fibrosis. ( 28495695 )
2017
10
CENTRAL RETINAL VEIN OCCLUSION IN GATA2 DEFICIENCY. ( 28248742 )
2017
11
Somatic mutations in children with GATA2-associated myelodysplastic syndrome who lack other features of GATA2 deficiency. ( 29296959 )
2017
12
Association of pulmonary alveolar proteinosis and fibrosis: patient with GATA2 deficiency. ( 27799394 )
2016
13
Association of GATA2 Deficiency With Severe Primary Epstein-Barr Virus (EBV) Infection and EBV-associated Cancers. ( 27169477 )
2016
14
Mediastinal and Disseminated Mycobacterium kansasii Disease in GATA2 Deficiency. ( 27607353 )
2016
15
GATA2 deficiency underlying severe blastomycosis and fatal herpes simplex virus-associated hemophagocytic lymphohistiocytosis. ( 26395816 )
2016
16
Merkel cell carcinoma in a patient with GATA2 deficiency: a novel association with primary immunodeficiency. ( 26252413 )
2016
17
Adenosine deaminase type 2 deficiency masquerading as GATA2 deficiency: Successful hematopoietic stem cell transplantation. ( 27130863 )
2016
18
Timely follow-up of a GATA2 deficiency patient allows successful treatment. ( 27481672 )
2016
19
GATA2 deficiency in children and adults with severe pulmonary alveolar proteinosis and hematologic disorders. ( 26264606 )
2015
20
GATA2 deficiency-associated bone marrow disorder differs from idiopathic aplastic anemia. ( 25359990 )
2015
21
[GATA2 deficiency]. ( 25509816 )
2014
22
GATA2 deficiency: a protean disorder of hematopoiesis, lymphatics, and immunity. ( 24227816 )
2014
23
Presence of hypogammaglobulinemia and abnormal antibody responses in GATA2 deficiency. ( 24726394 )
2014
24
Successful allogeneic hematopoietic stem cell transplantation for GATA2 deficiency. ( 21816832 )
2011

Variations for Immunodeficiency 21

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

75
# 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 top 50) (show all 347)
# Gene Variation Type Significance SNP ID Assembly Location
1 GATA2 NM_032638.4(GATA2): c.1192C> T (p.Arg398Trp) single nucleotide variant Pathogenic rs387906629 GRCh37 Chromosome 3, 128200113: 128200113
2 GATA2 NM_032638.4(GATA2): c.1192C> T (p.Arg398Trp) single nucleotide variant Pathogenic rs387906629 GRCh38 Chromosome 3, 128481270: 128481270
3 GATA2 NM_001145661.1(GATA2): c.761C> T (p.Pro254Leu) single nucleotide variant Pathogenic rs387906630 GRCh37 Chromosome 3, 128204680: 128204680
4 GATA2 NM_001145661.1(GATA2): c.761C> T (p.Pro254Leu) single nucleotide variant Pathogenic rs387906630 GRCh38 Chromosome 3, 128485837: 128485837
5 GATA2 NM_032638.4(GATA2): c.1061C> T (p.Thr354Met) single nucleotide variant Pathogenic rs387906631 GRCh37 Chromosome 3, 128200744: 128200744
6 GATA2 NM_032638.4(GATA2): c.1061C> T (p.Thr354Met) single nucleotide variant Pathogenic rs387906631 GRCh38 Chromosome 3, 128481901: 128481901
7 GATA2 NM_001145661.1(GATA2): c.-200_871+527del2032 deletion Pathogenic GRCh38 Chromosome 3, 128485200: 128487231
8 GATA2 NM_001145661.1(GATA2): c.1084_1095delCGAAACGCCAAC (p.Arg362_Asn365del) deletion Pathogenic rs869320734 GRCh37 Chromosome 3, 128200710: 128200721
9 GATA2 NM_001145661.1(GATA2): c.1084_1095delCGAAACGCCAAC (p.Arg362_Asn365del) deletion Pathogenic rs869320734 GRCh38 Chromosome 3, 128481867: 128481878
10 GATA2 NM_001145661.1(GATA2): c.243delAinsGC (p.Gly82Argfs) indel Pathogenic rs869320735 GRCh37 Chromosome 3, 128205198: 128205198
11 GATA2 NM_001145661.1(GATA2): c.243delAinsGC (p.Gly82Argfs) indel Pathogenic rs869320735 GRCh38 Chromosome 3, 128486355: 128486355
12 GATA2 NM_032638.4(GATA2): c.599dupG (p.Ser201Terfs) duplication Pathogenic rs768767517 GRCh37 Chromosome 3, 128204842: 128204842
13 GATA2 NM_032638.4(GATA2): c.599dupG (p.Ser201Terfs) duplication Pathogenic rs768767517 GRCh38 Chromosome 3, 128485999: 128485999
14 GATA2 NM_001145661.1(GATA2): c.1018-1G> T single nucleotide variant Pathogenic rs869320668 GRCh37 Chromosome 3, 128200788: 128200788
15 GATA2 NM_001145661.1(GATA2): c.1018-1G> T single nucleotide variant Pathogenic rs869320668 GRCh38 Chromosome 3, 128481945: 128481945
16 GATA2 NM_001145661.1(GATA2): c.1017+513_1017+540del28 deletion Pathogenic GRCh37 Chromosome 3, 128202163: 128202190
17 GATA2 NM_001145661.1(GATA2): c.1017+513_1017+540del28 deletion Pathogenic GRCh38 Chromosome 3, 128483320: 128483347
18 GATA2 NM_032638.4(GATA2): c.371C> A (p.Thr124Lys) single nucleotide variant Uncertain significance rs569301892 GRCh37 Chromosome 3, 128205070: 128205070
19 GATA2 NM_032638.4(GATA2): c.371C> A (p.Thr124Lys) single nucleotide variant Uncertain significance rs569301892 GRCh38 Chromosome 3, 128486227: 128486227
20 GATA2 NM_032638.4(GATA2): c.481C> G (p.Pro161Ala) single nucleotide variant Benign/Likely benign rs34799090 GRCh37 Chromosome 3, 128204960: 128204960
21 GATA2 NM_032638.4(GATA2): c.481C> G (p.Pro161Ala) single nucleotide variant Benign/Likely benign rs34799090 GRCh38 Chromosome 3, 128486117: 128486117
22 GATA2 NM_001145661.1(GATA2): c.748C> G (p.Pro250Ala) single nucleotide variant Benign/Likely benign rs78245253 GRCh37 Chromosome 3, 128204693: 128204693
23 GATA2 NM_001145661.1(GATA2): c.748C> G (p.Pro250Ala) single nucleotide variant Benign/Likely benign rs78245253 GRCh38 Chromosome 3, 128485850: 128485850
24 GATA2 NM_032638.4(GATA2): c.787G> A (p.Gly263Arg) single nucleotide variant Uncertain significance rs587778378 GRCh37 Chromosome 3, 128204654: 128204654
25 GATA2 NM_032638.4(GATA2): c.787G> A (p.Gly263Arg) single nucleotide variant Uncertain significance rs587778378 GRCh38 Chromosome 3, 128485811: 128485811
26 GATA2 NM_032638.4(GATA2): c.1113C> A (p.Asn371Lys) single nucleotide variant Likely pathogenic rs376003468 GRCh38 Chromosome 3, 128481849: 128481849
27 GATA2 NM_032638.4(GATA2): c.1113C> A (p.Asn371Lys) single nucleotide variant Likely pathogenic rs376003468 GRCh37 Chromosome 3, 128200692: 128200692
28 GATA2 NM_032638.4(GATA2): c.1021_1024dupGCCG (p.Ala342Glyfs) duplication Likely pathogenic rs869320770 GRCh38 Chromosome 3, 128481938: 128481941
29 GATA2 NM_032638.4(GATA2): c.1021_1024dupGCCG (p.Ala342Glyfs) duplication Likely pathogenic rs869320770 GRCh37 Chromosome 3, 128200781: 128200784
30 GATA2 NM_032638.4(GATA2): c.*183C> T single nucleotide variant Benign/Likely benign rs45598538 GRCh37 Chromosome 3, 128199679: 128199679
31 GATA2 NM_032638.4(GATA2): c.*183C> T single nucleotide variant Benign/Likely benign rs45598538 GRCh38 Chromosome 3, 128480836: 128480836
32 GATA2 NM_032638.4(GATA2): c.1410C> T (p.Pro470=) single nucleotide variant Likely benign rs878855169 GRCh37 Chromosome 3, 128199895: 128199895
33 GATA2 NM_032638.4(GATA2): c.1410C> T (p.Pro470=) single nucleotide variant Likely benign rs878855169 GRCh38 Chromosome 3, 128481052: 128481052
34 GATA2 NM_032638.4(GATA2): c.1359G> A (p.Leu453=) single nucleotide variant Likely benign rs878855168 GRCh37 Chromosome 3, 128199946: 128199946
35 GATA2 NM_032638.4(GATA2): c.1359G> A (p.Leu453=) single nucleotide variant Likely benign rs878855168 GRCh38 Chromosome 3, 128481103: 128481103
36 GATA2 NM_032638.4(GATA2): c.1144-6C> T single nucleotide variant Likely benign rs878855167 GRCh37 Chromosome 3, 128200167: 128200167
37 GATA2 NM_032638.4(GATA2): c.1144-6C> T single nucleotide variant Likely benign rs878855167 GRCh38 Chromosome 3, 128481324: 128481324
38 GATA2 NM_032638.4(GATA2): c.1035C> G (p.Ala345=) single nucleotide variant Likely benign rs371599112 GRCh37 Chromosome 3, 128200770: 128200770
39 GATA2 NM_032638.4(GATA2): c.1035C> G (p.Ala345=) single nucleotide variant Likely benign rs371599112 GRCh38 Chromosome 3, 128481927: 128481927
40 GATA2 NM_032638.4(GATA2): c.1017+8C> T single nucleotide variant Likely benign rs200848213 GRCh37 Chromosome 3, 128202695: 128202695
41 GATA2 NM_032638.4(GATA2): c.1017+8C> T single nucleotide variant Likely benign rs200848213 GRCh38 Chromosome 3, 128483852: 128483852
42 GATA2 NM_032638.4(GATA2): c.279G> A (p.Pro93=) single nucleotide variant Benign rs142993548 GRCh37 Chromosome 3, 128205162: 128205162
43 GATA2 NM_032638.4(GATA2): c.279G> A (p.Pro93=) single nucleotide variant Benign rs142993548 GRCh38 Chromosome 3, 128486319: 128486319
44 GATA2 NM_032638.4(GATA2): c.182C> T (p.Ala61Val) single nucleotide variant Uncertain significance rs375349195 GRCh38 Chromosome 3, 128486850: 128486850
45 GATA2 NM_032638.4(GATA2): c.182C> T (p.Ala61Val) single nucleotide variant Uncertain significance rs375349195 GRCh37 Chromosome 3, 128205693: 128205693
46 GATA2 NM_032638.4(GATA2): c.142T> A (p.Phe48Ile) single nucleotide variant Uncertain significance rs878855170 GRCh37 Chromosome 3, 128205733: 128205733
47 GATA2 NM_032638.4(GATA2): c.142T> A (p.Phe48Ile) single nucleotide variant Uncertain significance rs878855170 GRCh38 Chromosome 3, 128486890: 128486890
48 GATA2 NM_032638.4(GATA2): c.136G> A (p.Asp46Asn) single nucleotide variant Uncertain significance rs370750401 GRCh37 Chromosome 3, 128205739: 128205739
49 GATA2 NM_032638.4(GATA2): c.136G> A (p.Asp46Asn) single nucleotide variant Uncertain significance rs370750401 GRCh38 Chromosome 3, 128486896: 128486896
50 GATA2 NM_032638.4(GATA2): c.121C> G (p.Pro41Ala) single nucleotide variant Conflicting interpretations of pathogenicity rs143590990 GRCh37 Chromosome 3, 128205754: 128205754

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
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
Content
Loading form....