MCID: IMM078
MIFTS: 37

Immunodeficiency 21

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


External Ids:

OMIM 57 614172
Orphanet 59 ORPHA228423
ICD10 via Orphanet 34 D72.8
MedGen 42 C3280030
MeSH 44 D008231
UMLS 73 C3280030

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 hematopoietic stem cell transplantation and pulmonary alveolar proteinosis. 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 marrow, and related phenotypes are neutropenia and aplastic anemia

NIH Rare Diseases : 53 GATA2 deficiency is a rare genetic disease that can present as several distinct syndromes: dendritic cell, monocyte, B, and natural killer lymphoid deficiency (monocytopenia and mycobacterial infection syndrome); familial myelodysplastic syndromes (MDS)/acute myeloid leukemia (AML); deafness-lymphedema-leukemia syndrome (Emberger syndrome); or natural killer (NK) cell deficiency. Symptoms are varied and include severe infections (most commonly viral or nontuberculous mycobacterial infections), respiratory problems, hearing loss, leg swelling, and cancer that can appear early in childhood but also later on in life (such as myelodysplasia, acute myeloid leukemia (AML) or chronic myelomonocytic leukemia).  It is caused by mutations in the GATA2 gene, which provides instructions to produce GATA2, a protein that controls when certain genes are “turned on,” and directs the activity of many types of cells, including immune cells. Mutations in the GATA2 gene result in impaired GATA2 protein function leading to GATA2 deficiency. Inheritance is autosomal dominant. Treatment depends on the symptoms and may include vaccination, antibiotics, and bone marrow transplant. 

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

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 10.1
2 pulmonary alveolar proteinosis 10.0
3 lymphedema 10.0
4 pulmonary hypertension 9.9
5 leukemia, acute myeloid 9.9
6 myeloid leukemia 9.9
7 aplastic anemia 9.8
8 lymphedema, primary, with myelodysplasia 9.8
9 pulmonary fibrosis and/or bone marrow failure, telomere-related, 2 9.8
10 hemophagocytic lymphohistiocytosis 9.8
11 blastomycosis 9.8

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 8)
# Description HPO Frequency HPO Source Accession
1 neutropenia 32 HP:0001875
2 aplastic anemia 32 occasional (7.5%) HP:0001915
3 immunodeficiency 32 HP:0002721
4 recurrent fungal infections 32 HP:0002841
5 recurrent viral infections 32 HP:0004429
6 recurrent mycobacterium avium complex infections 32 HP:0011275
7 abnormal natural killer cell morphology 32 HP:0012176
8 monocytopenia 32 HP:0012312

Drugs & Therapeutics for Immunodeficiency 21

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

(show all 14)
# 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 Antineoplastic Agents, Alkylating Phase 2
9 Antirheumatic Agents Phase 2
10 Immunosuppressive Agents Phase 2
11 Antibodies
12 Autoantibodies
13 Immunoglobulins
14 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)
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 Marrow, Bone, T Cells, Nk Cells, Testes

Publications for Immunodeficiency 21

Articles related to Immunodeficiency 21:

(show all 15)
# 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
Successful Myeloablative Matched Unrelated Donor Hematopoietic Stem Cell Transplantation in a Young Girl With GATA2 Deficiency and Emberger Syndrome. ( 28234738 )
2017
5
Vulvar lymphedema and refractory VIN-III heralding GATA2 deficiency syndrome. ( 28947108 )
2017
6
Haemodynamically proven pulmonary hypertension in a patient with GATA2 deficiency-associated pulmonary alveolar proteinosis and fibrosis. ( 28495695 )
2017
7
Association of pulmonary alveolar proteinosis and fibrosis: patient with GATA2 deficiency. ( 27799394 )
2016
8
Association of GATA2 Deficiency With Severe Primary Epstein-Barr Virus (EBV) Infection and EBV-associated Cancers. ( 27169477 )
2016
9
Mediastinal and Disseminated Mycobacterium kansasii Disease in GATA2 Deficiency. ( 27607353 )
2016
10
GATA2 deficiency in children and adults with severe pulmonary alveolar proteinosis and hematologic disorders. ( 26264606 )
2015
11
GATA2 deficiency underlying severe blastomycosis and fatal herpes simplex virus-associated hemophagocytic lymphohistiocytosis. ( 26395816 )
2015
12
[GATA2 deficiency]. ( 25509816 )
2014
13
GATA2 deficiency: a protean disorder of hematopoiesis, lymphatics, and immunity. ( 24227816 )
2014
14
GATA2 deficiency-associated bone marrow disorder differs from idiopathic aplastic anemia. ( 25359990 )
2014
15
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 281)
# 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_001145661.1(GATA2): c.1061C> T (p.Thr354Met) single nucleotide variant Pathogenic/Likely pathogenic,risk factor rs387906631 GRCh37 Chromosome 3, 128200744: 128200744
6 GATA2 NM_001145661.1(GATA2): c.1061C> T (p.Thr354Met) single nucleotide variant Pathogenic/Likely pathogenic,risk factor 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.1113C> A (p.Asn371Lys) single nucleotide variant Likely pathogenic rs376003468 GRCh38 Chromosome 3, 128481849: 128481849
19 GATA2 NM_032638.4(GATA2): c.1113C> A (p.Asn371Lys) single nucleotide variant Likely pathogenic rs376003468 GRCh37 Chromosome 3, 128200692: 128200692
20 GATA2 NM_001145661.1(GATA2): c.1021_1024dupGCCG (p.Ala342Glyfs) duplication Pathogenic rs869320770 GRCh38 Chromosome 3, 128481938: 128481941
21 GATA2 NM_001145661.1(GATA2): c.1021_1024dupGCCG (p.Ala342Glyfs) duplication Pathogenic rs869320770 GRCh37 Chromosome 3, 128200781: 128200784
22 GATA2 NM_032638.4(GATA2): c.*183C> T single nucleotide variant Benign/Likely benign rs45598538 GRCh37 Chromosome 3, 128199679: 128199679
23 GATA2 NM_032638.4(GATA2): c.*183C> T single nucleotide variant Benign/Likely benign rs45598538 GRCh38 Chromosome 3, 128480836: 128480836
24 GATA2 NM_032638.4(GATA2): c.1410C> T (p.Pro470=) single nucleotide variant Likely benign rs878855169 GRCh37 Chromosome 3, 128199895: 128199895
25 GATA2 NM_032638.4(GATA2): c.1410C> T (p.Pro470=) single nucleotide variant Likely benign rs878855169 GRCh38 Chromosome 3, 128481052: 128481052
26 GATA2 NM_032638.4(GATA2): c.1359G> A (p.Leu453=) single nucleotide variant Likely benign rs878855168 GRCh37 Chromosome 3, 128199946: 128199946
27 GATA2 NM_032638.4(GATA2): c.1359G> A (p.Leu453=) single nucleotide variant Likely benign rs878855168 GRCh38 Chromosome 3, 128481103: 128481103
28 GATA2 NM_032638.4(GATA2): c.1144-6C> T single nucleotide variant Likely benign rs878855167 GRCh37 Chromosome 3, 128200167: 128200167
29 GATA2 NM_032638.4(GATA2): c.1144-6C> T single nucleotide variant Likely benign rs878855167 GRCh38 Chromosome 3, 128481324: 128481324
30 GATA2 NM_032638.4(GATA2): c.1035C> G (p.Ala345=) single nucleotide variant Likely benign rs371599112 GRCh37 Chromosome 3, 128200770: 128200770
31 GATA2 NM_032638.4(GATA2): c.1035C> G (p.Ala345=) single nucleotide variant Likely benign rs371599112 GRCh38 Chromosome 3, 128481927: 128481927
32 GATA2 NM_032638.4(GATA2): c.1017+8C> T single nucleotide variant Likely benign rs200848213 GRCh37 Chromosome 3, 128202695: 128202695
33 GATA2 NM_032638.4(GATA2): c.1017+8C> T single nucleotide variant Likely benign rs200848213 GRCh38 Chromosome 3, 128483852: 128483852
34 GATA2 NM_032638.4(GATA2): c.279G> A (p.Pro93=) single nucleotide variant Benign rs142993548 GRCh37 Chromosome 3, 128205162: 128205162
35 GATA2 NM_032638.4(GATA2): c.279G> A (p.Pro93=) single nucleotide variant Benign rs142993548 GRCh38 Chromosome 3, 128486319: 128486319
36 GATA2 NM_032638.4(GATA2): c.182C> T (p.Ala61Val) single nucleotide variant Uncertain significance rs375349195 GRCh38 Chromosome 3, 128486850: 128486850
37 GATA2 NM_032638.4(GATA2): c.182C> T (p.Ala61Val) single nucleotide variant Uncertain significance rs375349195 GRCh37 Chromosome 3, 128205693: 128205693
38 GATA2 NM_032638.4(GATA2): c.142T> A (p.Phe48Ile) single nucleotide variant Uncertain significance rs878855170 GRCh37 Chromosome 3, 128205733: 128205733
39 GATA2 NM_032638.4(GATA2): c.142T> A (p.Phe48Ile) single nucleotide variant Uncertain significance rs878855170 GRCh38 Chromosome 3, 128486890: 128486890
40 GATA2 NM_032638.4(GATA2): c.136G> A (p.Asp46Asn) single nucleotide variant Uncertain significance rs370750401 GRCh37 Chromosome 3, 128205739: 128205739
41 GATA2 NM_032638.4(GATA2): c.136G> A (p.Asp46Asn) single nucleotide variant Uncertain significance rs370750401 GRCh38 Chromosome 3, 128486896: 128486896
42 GATA2 NM_032638.4(GATA2): c.121C> G (p.Pro41Ala) single nucleotide variant Conflicting interpretations of pathogenicity rs143590990 GRCh37 Chromosome 3, 128205754: 128205754
43 GATA2 NM_032638.4(GATA2): c.121C> G (p.Pro41Ala) single nucleotide variant Conflicting interpretations of pathogenicity rs143590990 GRCh38 Chromosome 3, 128486911: 128486911
44 GATA2 NM_001145661.1(GATA2): c.1233G> A (p.Ala411=) single nucleotide variant Benign/Likely benign rs34172218 GRCh37 Chromosome 3, 128200072: 128200072
45 GATA2 NM_001145661.1(GATA2): c.1233G> A (p.Ala411=) single nucleotide variant Benign/Likely benign rs34172218 GRCh38 Chromosome 3, 128481229: 128481229
46 GATA2 NM_001145661.1(GATA2): c.564G> C (p.Thr188=) single nucleotide variant Benign/Likely benign rs34870876 GRCh37 Chromosome 3, 128204877: 128204877
47 GATA2 NM_001145661.1(GATA2): c.564G> C (p.Thr188=) single nucleotide variant Benign/Likely benign rs34870876 GRCh38 Chromosome 3, 128486034: 128486034
48 GATA2 NM_001145661.1(GATA2): c.480C> T (p.Thr160=) single nucleotide variant Benign/Likely benign rs199640729 GRCh37 Chromosome 3, 128204961: 128204961
49 GATA2 NM_001145661.1(GATA2): c.480C> T (p.Thr160=) single nucleotide variant Benign/Likely benign rs199640729 GRCh38 Chromosome 3, 128486118: 128486118
50 GATA2 NM_001145661.1(GATA2): c.333C> T (p.His111=) single nucleotide variant Benign rs148554346 GRCh37 Chromosome 3, 128205108: 128205108

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

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7 CNVD
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62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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