IMD68
MCID: IMM224
MIFTS: 36

Immunodeficiency 68 (IMD68)

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

Aliases & Classifications for Immunodeficiency 68

MalaCards integrated aliases for Immunodeficiency 68:

Name: Immunodeficiency 68 57 73
Myd88 Deficiency 57 20 43 73 29 6 39
Pyogenic Bacterial Infections, Recurrent, Due to Myd88 Deficiency 36 13
Bacterial Susceptibility Due to Tlr Signaling Pathway Deficiency 20 58
Pyogenic Bacterial Infections Due to Myd88 Deficiency 20 43
Myd88d 57 73
Imd68 57 73
Myd88 Deficiency; Myd88d 57

Characteristics:

Orphanet epidemiological data:

58
bacterial susceptibility due to tlr signaling pathway deficiency
Inheritance: Autosomal recessive; Age of onset: Childhood; Age of death: adolescent,late childhood;

OMIM®:

57 (Updated 05-Mar-2021)
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy or early childhood
bacterial meningitis is often an initial infection
high death rate before age 8 years
the disease tends to abate with age
treatment with ivig or prophylactic antibiotics may be beneficial


HPO:

31
immunodeficiency 68:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare immunological diseases


External Ids:

OMIM® 57 612260
OMIM Phenotypic Series 57 PS300755
KEGG 36 H00721
MeSH 44 D007153
ICD10 via Orphanet 33 D84.8
UMLS via Orphanet 72 C2677092
Orphanet 58 ORPHA183713
MedGen 41 C2677092

Summaries for Immunodeficiency 68

OMIM® : 57 Immunodeficiency-68 (IMD68) is an autosomal recessive primary immunodeficiency characterized by severe systemic and invasive bacterial infections beginning in infancy or early childhood. The most common organisms implicated are Streptococcus pneumoniae, Staphylococcus aureus, and Pseudomonas, although other organisms may be observed. IMD68 is life-threatening in infancy and early childhood. The first invasive infection typically occurs before 2 years of age, with meningitis and upper respiratory infections being common manifestations. The mortality rate in early childhood is high, with most deaths occurring before 8 years of age. Affected individuals have an impaired inflammatory response to infection, including lack of fever and neutropenia, although erythrocyte sedimentation rate (ESR) and C-reactive protein may be elevated. General immunologic workup tends to be normal, with normal levels of B cells, T cells, and NK cells. However, more detailed studies indicate impaired cytokine response to lipopolysaccharide (LPS) and IL1B (147720) stimulation; response to TNFA (191160) is usually normal. Patients have good antibody responses to most vaccinations. Viral, fungal, and parasitic infections are generally not observed. Early detection is critical in early childhood because prophylactic treatment with IVIg or certain antibiotics is effective; the disorder tends to improve naturally around adolescence. At the molecular level, IMD68 results from impaired function of selective Toll receptor (see TLR4, 603030)/IL1R (see IL1R1; 147810) signaling pathways that ultimately activate NFKB (164011) to produce cytokines (summary by Picard et al., 2010). See also IMD67 (607676), caused by mutation in the IRAK4 gene (602170), which shows a similar phenotype to IMD68. As the MYD88 and IRAK4 genes interact in the same intracellular signaling pathway, the clinical and cellular features are almost indistinguishable (summary by Picard et al., 2010). (612260) (Updated 05-Mar-2021)

MalaCards based summary : Immunodeficiency 68, also known as myd88 deficiency, is related to immunodeficiency 67 and bacterial infectious disease. An important gene associated with Immunodeficiency 68 is MYD88 (MYD88 Innate Immune Signal Transduction Adaptor), and among its related pathways/superpathways are Apoptosis and Toll-like receptor signaling pathway. Affiliated tissues include t cells, b cells and nk cells, and related phenotypes are immunodeficiency and recurrent bacterial skin infections

MedlinePlus Genetics : 43 MyD88 deficiency is an inherited disorder of the immune system (primary immunodeficiency). This primary immunodeficiency affects the innate immune response, which is the body's early, nonspecific response to foreign invaders (pathogens). MyD88 deficiency leads to abnormally frequent and severe infections by a subset of bacteria known as pyogenic bacteria. (Infection with pyogenic bacteria causes the production of pus.) However, affected individuals have normal resistance to other common bacteria, viruses, fungi, and parasites. The most common infections in MyD88 deficiency are caused by the Streptococcus pneumoniae, Staphylococcus aureus, and Pseudomonas aeruginosa bacteria. Most people with this condition have their first bacterial infection before age 2, and the infections can be life-threatening in infancy and childhood. Infections become less frequent by about age 10.Children with MyD88 deficiency develop invasive bacterial infections, which can involve the blood (septicemia), the membrane covering the brain and spinal cord (meningitis), or the joints (leading to inflammation and arthritis). Invasive infections can also cause areas of tissue breakdown and pus production (abscesses) on internal organs. In addition, affected individuals can have localized infections of the ears, nose, or throat. Although fever is a common reaction to bacterial infections, many people with MyD88 deficiency do not at first develop a high fever in response to these infections, even if the infection is severe.

GARD : 20 MYD88 deficiency is a rare primary immunodeficiency characterized by an increased susceptibility to certain types of bacterial infections. People affected by this condition generally have abnormally frequent and life-threatening infections caused by pyogenic bacteria (such as Streptococcus pneumoniae, Staphylococcus aureus, and Pseudomonas aeruginosa). However, their immune response to other common bacteria, viruses, fungi, and parasites is normal. MYD88 deficiency is caused by changes (mutations) in the MYD88 gene and is inherited in an autosomal recessive manner. Management is focused on the prevention and early treatment of infections with appropriate antibiotics.

KEGG : 36 Autosomal recessive MyD88 deficiency predisposes affected patients to recurrent pyogenic bacterial infections, including invasive pneumococcal disease. The patients are resistant to other microbes.

UniProtKB/Swiss-Prot : 73 Immunodeficiency 68: An autosomal recessive primary immunodeficiency characterized by life- threatening, often recurrent, pyogenic bacterial infections, including invasive pneumococcal disease, beginning in infancy or early childhood.

Related Diseases for Immunodeficiency 68

Diseases related to Immunodeficiency 68 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 18)
# Related Disease Score Top Affiliating Genes
1 immunodeficiency 67 10.9
2 bacterial infectious disease 10.0
3 aortic aneurysm, familial abdominal, 1 9.8
4 dermatitis, atopic 9.8
5 graft-versus-host disease 9.8
6 disease by infectious agent 9.8
7 chlamydia 9.8
8 lyme disease 9.8
9 lymphadenitis 9.8
10 plague 9.8
11 aortic aneurysm 9.8
12 syphilis 9.8
13 eye disease 9.8
14 lung disease 9.8
15 amyloidosis 9.8
16 acute graft versus host disease 9.8
17 cytokine deficiency 9.8
18 aneurysm 9.8

Graphical network of the top 20 diseases related to Immunodeficiency 68:



Diseases related to Immunodeficiency 68

Symptoms & Phenotypes for Immunodeficiency 68

Human phenotypes related to Immunodeficiency 68:

58 31 (show all 11)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 immunodeficiency 58 31 hallmark (90%) Very frequent (99-80%) HP:0002721
2 recurrent bacterial skin infections 58 31 frequent (33%) Frequent (79-30%) HP:0005406
3 fever 58 31 occasional (7.5%) Occasional (29-5%) HP:0001945
4 sepsis 31 very rare (1%) HP:0100806
5 abscess 31 very rare (1%) HP:0025615
6 septic arthritis 31 very rare (1%) HP:0003095
7 recurrent skin infections 31 very rare (1%) HP:0001581
8 b lymphocytopenia 31 very rare (1%) HP:0010976
9 delayed umbilical cord separation 31 very rare (1%) HP:0032434
10 recurrent meningitis 31 very rare (1%) HP:0006946
11 lymphadenitis 31 HP:0002840

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Mar-2021)
Immunology:
neutropenia
recurrent invasive bacterial infections
streptococcus pneumonia
staphylococcus aureus
pseudomonas aeruginosa
more
Respiratory:
adenitis
upper respiratory tract infections

Neurologic Central Nervous System:
bacterial meningitis

Laboratory Abnormalities:
variable c-reactive protein
variable esr

Respiratory Nasopharynx:
pharyngitis

Prenatal Manifestations Placenta And Umbilical Cord:
delayed umbilical cord separation

Metabolic Features:
no or attenuated fever

Clinical features from OMIM®:

612260 (Updated 05-Mar-2021)

Drugs & Therapeutics for Immunodeficiency 68

Search Clinical Trials , NIH Clinical Center for Immunodeficiency 68

Genetic Tests for Immunodeficiency 68

Genetic tests related to Immunodeficiency 68:

# Genetic test Affiliating Genes
1 Myd88 Deficiency 29 MYD88

Anatomical Context for Immunodeficiency 68

MalaCards organs/tissues related to Immunodeficiency 68:

40
T Cells, B Cells, Nk Cells, Spinal Cord, Myeloid, Bone Marrow, Bone

Publications for Immunodeficiency 68

Articles related to Immunodeficiency 68:

(show top 50) (show all 124)
# Title Authors PMID Year
1
A novel truncating mutation in MYD88 in a patient with BCG adenitis, neutropenia and delayed umbilical cord separation. 6 57 61
31301515 2019
2
Clinical features and outcome of patients with IRAK-4 and MyD88 deficiency. 6 57 61
21057262 2010
3
Myeloid differentiation primary response gene 88 (MyD88) deficiency in a large kindred. 61 6 57
20538326 2010
4
Pyogenic bacterial infections in humans with MyD88 deficiency. 6 57 61
18669862 2008
5
The adapter protein Myd88 plays an important role in limiting mycobacterial growth in a zebrafish model for tuberculosis. 61
33559740 2021
6
MyD88 in myofibroblasts enhances colitis-associated tumorigenesis via promoting macrophage M2 polarization. 61
33535045 2021
7
Abnormal brain structure and behavior in MyD88-deficient mice. 61
33002631 2021
8
A small molecule inhibitor of MyD88 exhibits broad spectrum antiviral activity by up regulation of type I interferon. 61
32621945 2020
9
MyD88-dependent signaling in non-parenchymal cells promotes liver carcinogenesis. 61
30770929 2020
10
Modeling MyD88 Deficiency In Vitro Provides New Insights in Its Function. 61
33424861 2020
11
Increased LIGHT expression and activation of non-canonical NF-κB are observed in gastric lesions of MyD88-deficient mice upon Helicobacter felis infection. 61
31065023 2019
12
Epithelium-specific MyD88 signaling, but not DCs or macrophages, control acute intestinal infection with Clostridium difficile. 61
30802297 2019
13
ST2/MyD88 Deficiency Protects Mice against Acute Graft-versus-Host Disease and Spares Regulatory T Cells. 61
30979817 2019
14
Innate immune adaptor MyD88 deficiency prevents skin inflammation in SHARPIN-deficient mice. 61
30038386 2019
15
Oxidized LDL upregulates macrophage DPP4 expression via TLR4/TRIF/CD36 pathways. 61
30738832 2019
16
MyD88 controls airway epithelial Muc5ac expression during TLR activation conditions from agricultural organic dust exposure. 61
30358438 2019
17
TLR-2 and MyD88-Dependent Activation of MAPK and STAT Proteins Regulates Proinflammatory Cytokine Response and Immunity to Experimental Trypanosoma congolense Infection. 61
31824484 2019
18
Host MyD88 signaling protects against acute graft-versus-host disease after allogeneic bone marrow transplantation. 61
30317551 2019
19
Innate Sensing through Mesenchymal TLR4/MyD88 Signals Promotes Spontaneous Intestinal Tumorigenesis. 61
30650348 2019
20
First Case of Patient With Two Homozygous Mutations in MYD88 and CARD9 Genes Presenting With Pyogenic Bacterial Infections, Elevated IgE, and Persistent EBV Viremia. 61
30837984 2019
21
Innate immune adaptor TRIF deficiency accelerates disease progression of ALS mice with accumulation of aberrantly activated astrocytes. 61
29568058 2018
22
MyD88 signaling causes autoimmune sialadenitis through formation of high endothelial venules and upregulation of LTβ receptor-mediated signaling. 61
30250175 2018
23
MyD88 activation in cardiomyocytes contributes to the heart immune response to acute Trypanosoma cruzi infection with no effect on local parasite control. 61
30067739 2018
24
MyD88 Deficiency Protects Against Dry Eye-Induced Damage. 61
30025110 2018
25
Chlamydia and Lipids Engage a Common Signaling Pathway That Promotes Atherogenesis. 61
29622163 2018
26
B Cells Producing Type I IFN Modulate Macrophage Polarization in Tuberculosis. 61
29161093 2018
27
Differential role of MyD88 and TRIF signaling in myeloid cells in the pathogenesis of autoimmune diabetes. 61
29522531 2018
28
Hematopoietic MyD88 and IL-18 are essential for IFN-γ-dependent restriction of type A Francisella tularensis infection. 61
28951422 2017
29
Mer Receptor Tyrosine Kinase Signaling Prevents Self-Ligand Sensing and Aberrant Selection in Germinal Centers. 61
29118245 2017
30
Role of MyD88 signaling in the imiquimod-induced mouse model of psoriasis: focus on innate myeloid cells. 61
28642279 2017
31
Basal autophagy prevents autoactivation or enhancement of inflammatory signals by targeting monomeric MyD88. 61
28432355 2017
32
General, but not myeloid or type II lung epithelial cell, myeloid differentiation factor 88 deficiency abrogates house dust mite induced allergic lung inflammation. 61
27625307 2017
33
HMGB1 translocation and release mediate cigarette smoke-induced pulmonary inflammation in mice through a TLR4/MyD88-dependent signaling pathway. 61
27807045 2017
34
TLR3 downregulates expression of schizophrenia gene Disc1 via MYD88 to control neuronal morphology. 61
27979975 2017
35
Short-term MyD88 inhibition ameliorates cardiac graft rejection and promotes donor-specific hyporesponsiveness of skin grafts in mice. 61
27125343 2016
36
Targeted next-generation sequencing revealed MYD88 deficiency in a child with chronic yersiniosis and granulomatous lymphadenitis. 61
26632527 2016
37
Requirement of MyD88 signaling in keratinocytes for Langerhans cell migration and initiation of atopic dermatitis-like symptoms in mice. 61
26694221 2016
38
Differential Effect of MyD88 Signal in Donor T Cells on Graft-versus-Leukemia Effect and Graft-versus-Host Disease after Experimental Allogeneic Stem Cell Transplantation. 61
26552489 2015
39
Recipient Myd88 Deficiency Promotes Spontaneous Resolution of Kidney Allograft Rejection. 61
25788530 2015
40
MyD88 Signaling Regulates Steady-State Migration of Intestinal CD103+ Dendritic Cells Independently of TNF-α and the Gut Microbiota. 61
26259586 2015
41
Myd88 Initiates Early Innate Immune Responses and Promotes CD4 T Cells during Coronavirus Encephalomyelitis. 61
26136579 2015
42
Natural Killer Cell Sensing of Infected Cells Compensates for MyD88 Deficiency but Not IFN-I Activity in Resistance to Mouse Cytomegalovirus. 61
25954804 2015
43
MyD88-dependent signaling drives host survival and early cytokine production during Histoplasma capsulatum infection. 61
25583527 2015
44
The importance of the Pseudomonas aeruginosa type III secretion system in epithelium traversal depends upon conditions of host susceptibility. 61
25667266 2015
45
MyD88 in macrophages is critical for abscess resolution in staphylococcal skin infection. 61
25681348 2015
46
Relevance of the myeloid differentiation factor 88 (MyD88) on RANKL, OPG, and nod expressions induced by TLR and IL-1R signaling in bone marrow stromal cells. 61
25125146 2015
47
A role for innate immunity in the development of hypertension. 61
25441337 2014
48
MyD88 acts as an adaptor protein for inflammatory signalling induced by amyloid-β in macrophages. 61
25124962 2014
49
B cell-intrinsic TLR7 signaling is essential for the development of spontaneous germinal centers. 61
25252960 2014
50
MyD88 is dispensable for cerebral amyloidosis and neuroinflammation in APP/PS1 transgenic mice. 61
25174876 2014

Variations for Immunodeficiency 68

ClinVar genetic disease variations for Immunodeficiency 68:

6 (show all 28)
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 MYD88 NM_002468.5(MYD88):c.586C>T (p.Arg196Cys) SNV Pathogenic 7495 rs137853064 3:38182001-38182001 3:38140510-38140510
2 MYD88 NM_002468.5(MYD88):c.278T>C (p.Leu93Pro) SNV Pathogenic 7496 rs137853065 3:38180469-38180469 3:38138978-38138978
3 MYD88 E66* Variation Pathogenic 929843
4 MYD88 NM_002468.5(MYD88):c.-24_-6del Deletion Pathogenic 469578 rs746651350 3:38180162-38180180 3:38138671-38138689
5 MYD88 NM_002468.5(MYD88):c.154_156GAG[1] (p.Glu53del) Microsatellite Likely pathogenic 235259 rs878852993 3:38180344-38180346 3:38138853-38138855
6 MYD88 NM_002468.5(MYD88):c.751C>T (p.Arg251Ter) SNV Uncertain significance 537300 rs748659894 3:38182637-38182637 3:38141146-38141146
7 MYD88 NM_002468.5(MYD88):c.-8C>G SNV Uncertain significance 961630 3:38180184-38180184 3:38138693-38138693
8 MYD88 NM_002468.5(MYD88):c.-30G>A SNV Uncertain significance 958926 3:38180162-38180162 3:38138671-38138671
9 MYD88 NM_002468.5(MYD88):c.458C>A (p.Pro153His) SNV Uncertain significance 953721 3:38181484-38181484 3:38139993-38139993
10 MYD88 NM_002468.5(MYD88):c.860C>T (p.Thr287Ile) SNV Uncertain significance 537302 rs138284536 3:38182746-38182746 3:38141255-38141255
11 MYD88 NM_002468.5(MYD88):c.499T>C (p.Tyr167His) SNV Uncertain significance 568203 rs186265242 3:38181914-38181914 3:38140423-38140423
12 MYD88 NM_002468.5(MYD88):c.511G>A (p.Asp171Asn) SNV Uncertain significance 574389 rs1559484615 3:38181926-38181926 3:38140435-38140435
13 MYD88 NM_002468.5(MYD88):c.113A>G (p.Asn38Ser) SNV Uncertain significance 639601 rs748676192 3:38180304-38180304 3:38138813-38138813
14 MYD88 NM_002468.5(MYD88):c.754C>G (p.Leu252Val) SNV Uncertain significance 653936 rs1575278069 3:38182640-38182640 3:38141149-38141149
15 MYD88 NM_002468.5(MYD88):c.212C>T (p.Thr71Ile) SNV Uncertain significance 660526 rs761035975 3:38180403-38180403 3:38138912-38138912
16 MYD88 NM_002468.5(MYD88):c.755T>C (p.Leu252Pro) SNV Uncertain significance 37055 rs387907272 3:38182641-38182641 3:38141150-38141150
17 MYD88 NM_002468.5(MYD88):c.-9C>G SNV Uncertain significance 134869 rs587778544 3:38180183-38180183 3:38138692-38138692
18 MYD88 NM_002468.5(MYD88):c.434C>A (p.Ala145Glu) SNV Uncertain significance 846019 3:38181460-38181460 3:38139969-38139969
19 MYD88 NM_002468.5(MYD88):c.479G>A (p.Arg160His) SNV Uncertain significance 838237 3:38181894-38181894 3:38140403-38140403
20 MYD88 NM_002468.5(MYD88):c.366G>T (p.Gln122His) SNV Uncertain significance 537301 rs372319724 3:38181392-38181392 3:38139901-38139901
21 MYD88 NM_002468.5(MYD88):c.106T>C (p.Phe36Leu) SNV Uncertain significance 537299 rs372072898 3:38180297-38180297 3:38138806-38138806
22 MYD88 NM_002468.5(MYD88):c.66G>T (p.Leu22=) SNV Likely benign 748869 rs765037478 3:38180257-38180257 3:38138766-38138766
23 MYD88 NM_002468.5(MYD88):c.604A>C (p.Thr202Pro) SNV Benign 469579 rs191826554 3:38182019-38182019 3:38140528-38140528
24 MYD88 NM_002468.5(MYD88):c.270C>G (p.Leu90=) SNV Benign 709850 rs143752366 3:38180461-38180461 3:38138970-38138970
25 MYD88 NM_002468.5(MYD88):c.80T>C (p.Met27Thr) SNV Benign 134871 rs201871349 3:38180271-38180271 3:38138780-38138780
26 MYD88 NM_002468.5(MYD88):c.644+3T>C SNV Benign 719591 rs148149492 3:38182062-38182062 3:38140571-38140571
27 MYD88 NM_002468.5(MYD88):c.261C>T (p.Gly87=) SNV Benign 537304 rs373382593 3:38180452-38180452 3:38138961-38138961
28 MYD88 NM_002468.5(MYD88):c.36C>G (p.Ala12=) SNV Benign 537305 rs79867863 3:38180227-38180227 3:38138736-38138736

UniProtKB/Swiss-Prot genetic disease variations for Immunodeficiency 68:

73
# Symbol AA change Variation ID SNP ID
1 MYD88 p.Leu93Pro VAR_047953 rs137853065
2 MYD88 p.Arg196Cys VAR_047954 rs137853064

Expression for Immunodeficiency 68

Search GEO for disease gene expression data for Immunodeficiency 68.

Pathways for Immunodeficiency 68

Pathways related to Immunodeficiency 68 according to KEGG:

36
# Name Kegg Source Accession
1 Apoptosis hsa04210
2 Toll-like receptor signaling pathway hsa04620

GO Terms for Immunodeficiency 68

Sources for Immunodeficiency 68

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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