MCID: IMM096
MIFTS: 21

Immunodeficiency 30

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

Aliases & Classifications for Immunodeficiency 30

MalaCards integrated aliases for Immunodeficiency 30:

Name: Immunodeficiency 30 57 75 29 6 73
Il12rb1 Deficiency 57 53 75
Mendelian Susceptibility to Mycobacterial Diseases Due to Complete Il12rb1 Deficiency 53 59
Mendelian Susceptibility to Interleukin 12 Receptor Beta 1 Deficiency 53 59
Msmd Due to Complete Interleukin 12 Receptor Beta 1 Deficiency 53 59
Msmd Due to Complete Il12rb1 Deficiency 53 59
Imd30 57 75
Mendelian Susceptibility to Mycobacterial Infections Due to Il12 Deficiency 53
Immunodeficiency, Type 30 40
Il-12râ1 Deficiency 53

Characteristics:

Orphanet epidemiological data:

59
mendelian susceptibility to mycobacterial diseases due to complete il12rb1 deficiency
Inheritance: Autosomal recessive; Age of onset: Childhood; Age of death: adult;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
onset usually in childhood after bcg vaccination


HPO:

32
immunodeficiency 30:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 59  
Rare immunological diseases


External Ids:

OMIM 57 614891
Orphanet 59 ORPHA319552
ICD10 via Orphanet 34 D84.8
SNOMED-CT via HPO 69 258211005 234532001
UMLS 73 C4013949

Summaries for Immunodeficiency 30

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 319552Disease definitionMendelian susceptibility to mycobacterial diseases (MSMD) due to complete interleukin-12 receptor subunit beta-1 (IL12RB1) deficiency is a genetic variant of MSMD (see this term) characterized by mild bacillus Calmette-Guérin (BCG) infections and recurrent Salmonella infections.EpidemiologyThe prevalence is unknown. Over 140 cases have been reported in the world.Clinical descriptionDisease onset usually occurs in patients before the age of 12 with the appearance of BCG disease, usually after receiving the vaccination. Over half of patients with this variant experience an additional infection with non-typhoidal Salmonella. Severe tuberculosis caused by Mycobacterium tuberculosis has been reported in several unrelated patients, providing the first documented evidence of a mendelian predisposition to tuberculosis. Other infections with Paracoccidiodes brasiliensis, Leishmania and Klebsiella have been reported in a single patient. Some patients also suffer from Candida infections. Most genetically affected siblings of index cases are asymptomatic, indicating low penetrance for case definition phenotypes.EtiologyMSMD due to complete IL12RB1 deficiency is caused by mutations in the IL12RB1 gene (19p13.1) subunit that encodes for the IL-12R-beta1 chain. These mutations impair the IL-12/IL-23 pathway essential for production of IFN-beta and the resulting immunity against Salmonella and BCG infections. Two clinically indistinguishable forms have been reported defined by the presence or absence of protein expression on the cell surface.Diagnostic methodsDiagnosis is made by laboratory analysis. In general, there is no expression of IL12RB1 at the surface of activated T-lymphocytes and NK cells. For the moment, only one mutation of IL12 RB1 leads to residual expression of the receptor on the cell surface. Low IFN-gamma levels are measured by ELISA after whole blood activation by BCG and BCG+IL-12. Genetic testing reveals mutations in IL12RB1. Impaired development of the Th17 cells is demonstrated in patients with this immunodeficiency.Differential diagnosisOther genetic etiologies of MSMD should be excluded.Antenatal diagnosisThis immunodeficiency is not severe and antenatal diagnosis is not necessary.Genetic counselingMSMD due to complete IL12RB1 deficiency is inherited in an autosomal recessive manner so genetic counseling is possible.Management and treatmentBCG vaccination should be avoided in those with a known mutation in the IL12RB1 gene. Treatment is usually attained from long term antimicrobial therapy combined with recombinant IFN-gamma. For those who have localized splenic/mesenteric lesions with poor drug penetration, surgical removal is indicated.PrognosisWith proper treatment the prognosis is usually good with most patients reaching adulthood.Visit the Orphanet disease page for more resources.

MalaCards based summary : Immunodeficiency 30, is also known as il12rb1 deficiency. An important gene associated with Immunodeficiency 30 is IL12RB1 (Interleukin 12 Receptor Subunit Beta 1). Affiliated tissues include nk cells, testes and whole blood, and related phenotypes are immunodeficiency and recurrent mycobacterial infections

OMIM : 57 IMD30 results from autosomal recessive IL12RB1 deficiency and is the most common form of susceptibility to mycobacterial disease. Activated T and natural killer lymphocytes from IMD30 patients do not express IL12RB1 on their surface or, more rarely, express nonfunctional IL12RB1 on their surface. IMD30 patients therefore lack responses to IL12 (see 161560) and IL23 (see 605580). The clinical presentation of IL12RB1-deficient patients is similar to that of IL12B-deficient patients (see IMD29, 614890). Bacillus Calmette-Guerin (BCG) disease and salmonellosis are the most frequent infections. Salmonellosis is present in about half of IL12RB1-deficient patients, and significant numbers of patients present with isolated salmonellosis. Severe tuberculosis has been reported in several unrelated patients, and other infections have been reported in single patients. IMD30 has low penetrance, and patients have relatively mild disease and good prognosis (review by Al-Muhsen and Casanova, 2008). (614891)

UniProtKB/Swiss-Prot : 75 Immunodeficiency 30: A form of Mendelian susceptibility to mycobacterial disease, a rare condition caused by impairment of interferon-gamma mediated immunity. It is characterized by predisposition to illness caused by moderately virulent mycobacterial species, such as Bacillus Calmette-Guerin (BCG) vaccine, environmental non-tuberculous mycobacteria, and by the more virulent Mycobacterium tuberculosis. Other microorganisms rarely cause severe clinical disease in individuals with susceptibility to mycobacterial infections, with the exception of Salmonella which infects less than 50% of these individuals. Clinical outcome severity depends on the degree of impairment of interferon-gamma mediated immunity. Some patients die of overwhelming mycobacterial disease with lepromatous-like lesions in early childhood, whereas others develop, later in life, disseminated but curable infections with tuberculoid granulomas. IMD30 has low penetrance, and affected individuals have relatively mild disease and good prognosis. BCG disease and salmonellosis are the most frequent infections in IMD30 patients.

Related Diseases for Immunodeficiency 30

Symptoms & Phenotypes for Immunodeficiency 30

Symptoms via clinical synopsis from OMIM:

57
Immunology:
increased susceptibility to systemic infections, particularly mycobacteria, candida, and salmonella
decreased or absent il12r-beta-1 expression on t cells
patient cells show no gamma-interferon response to il12


Clinical features from OMIM:

614891

Human phenotypes related to Immunodeficiency 30:

32
# Description HPO Frequency HPO Source Accession
1 immunodeficiency 32 HP:0002721
2 recurrent mycobacterial infections 32 HP:0011274

Drugs & Therapeutics for Immunodeficiency 30

Search Clinical Trials , NIH Clinical Center for Immunodeficiency 30

Genetic Tests for Immunodeficiency 30

Genetic tests related to Immunodeficiency 30:

# Genetic test Affiliating Genes
1 Immunodeficiency 30 29 IL12RB1

Anatomical Context for Immunodeficiency 30

MalaCards organs/tissues related to Immunodeficiency 30:

41
Nk Cells, Testes, Whole Blood, T Cells

Publications for Immunodeficiency 30

Articles related to Immunodeficiency 30:

# Title Authors Year
1
Disseminated BCG in an infant with interleukin-12 receptor B1 (IL12RB1) deficiency. ( 24863105 )
2014

Variations for Immunodeficiency 30

UniProtKB/Swiss-Prot genetic disease variations for Immunodeficiency 30:

75
# Symbol AA change Variation ID SNP ID
1 IL12RB1 p.Arg213Trp VAR_015577 rs121434494

ClinVar genetic disease variations for Immunodeficiency 30:

6
(show top 50) (show all 64)
# Gene Variation Type Significance SNP ID Assembly Location
1 IL12RB1 NM_005535.2(IL12RB1): c.94C> T (p.Gln32Ter) single nucleotide variant Pathogenic rs121434492 GRCh37 Chromosome 19, 18194272: 18194272
2 IL12RB1 NM_005535.2(IL12RB1): c.94C> T (p.Gln32Ter) single nucleotide variant Pathogenic rs121434492 GRCh38 Chromosome 19, 18083462: 18083462
3 IL12RB1 NM_005535.2(IL12RB1): c.1126C> T (p.Gln376Ter) single nucleotide variant Pathogenic rs121434493 GRCh37 Chromosome 19, 18180419: 18180419
4 IL12RB1 NM_005535.2(IL12RB1): c.1126C> T (p.Gln376Ter) single nucleotide variant Pathogenic rs121434493 GRCh38 Chromosome 19, 18069609: 18069609
5 IL12RB1 IL12RB1, 409-549DEL deletion Pathogenic
6 IL12RB1 NM_005535.2(IL12RB1): c.637C> T (p.Arg213Trp) single nucleotide variant Pathogenic rs121434494 GRCh37 Chromosome 19, 18186622: 18186622
7 IL12RB1 NM_005535.2(IL12RB1): c.637C> T (p.Arg213Trp) single nucleotide variant Pathogenic rs121434494 GRCh38 Chromosome 19, 18075812: 18075812
8 IL12RB1 NM_005535.2(IL12RB1): c.700+362_1619-944del deletion Pathogenic GRCh38 Chromosome 19, 18063221: 18075387
9 IL12RB1 NM_005535.2(IL12RB1): c.700+362_1619-944del deletion Pathogenic GRCh37 Chromosome 19, 18174031: 18186197
10 IL12RB1 NM_005535.2(IL12RB1): c.1021+1G> C single nucleotide variant Pathogenic rs587776680 GRCh38 Chromosome 19, 18072111: 18072111
11 IL12RB1 NM_005535.2(IL12RB1): c.1021+1G> C single nucleotide variant Pathogenic rs587776680 GRCh37 Chromosome 19, 18182921: 18182921
12 IL12RB1 NM_005535.2(IL12RB1): c.592T> C (p.Cys198Arg) single nucleotide variant Pathogenic rs121434495 GRCh37 Chromosome 19, 18186667: 18186667
13 IL12RB1 NM_005535.2(IL12RB1): c.592T> C (p.Cys198Arg) single nucleotide variant Pathogenic rs121434495 GRCh38 Chromosome 19, 18075857: 18075857
14 IL12RB1 IL12RB1, 3-BP DEL, EX10 deletion Pathogenic
15 IL12RB1 NM_005535.2(IL12RB1): c.1573G> A (p.Ala525Thr) single nucleotide variant Benign/Likely benign rs11575935 GRCh37 Chromosome 19, 18174731: 18174731
16 IL12RB1 NM_005535.2(IL12RB1): c.1573G> A (p.Ala525Thr) single nucleotide variant Benign/Likely benign rs11575935 GRCh38 Chromosome 19, 18063921: 18063921
17 IL12RB1 NM_005535.2(IL12RB1): c.1584G> A (p.Arg528=) single nucleotide variant Conflicting interpretations of pathogenicity rs141968777 GRCh37 Chromosome 19, 18174720: 18174720
18 IL12RB1 NM_005535.2(IL12RB1): c.1584G> A (p.Arg528=) single nucleotide variant Conflicting interpretations of pathogenicity rs141968777 GRCh38 Chromosome 19, 18063910: 18063910
19 IL12RB1 NM_005535.2(IL12RB1): c.1960G> A (p.Asp654Asn) single nucleotide variant Conflicting interpretations of pathogenicity rs202106699 GRCh37 Chromosome 19, 18170727: 18170727
20 IL12RB1 NM_005535.2(IL12RB1): c.1960G> A (p.Asp654Asn) single nucleotide variant Conflicting interpretations of pathogenicity rs202106699 GRCh38 Chromosome 19, 18059917: 18059917
21 IL12RB1 NM_005535.2(IL12RB1): c.1914T> C (p.Pro638=) single nucleotide variant Conflicting interpretations of pathogenicity rs199686420 GRCh37 Chromosome 19, 18170773: 18170773
22 IL12RB1 NM_005535.2(IL12RB1): c.1914T> C (p.Pro638=) single nucleotide variant Conflicting interpretations of pathogenicity rs199686420 GRCh38 Chromosome 19, 18059963: 18059963
23 IL12RB1 NM_005535.2(IL12RB1): c.1149C> T (p.Cys383=) single nucleotide variant Conflicting interpretations of pathogenicity rs17882216 GRCh38 Chromosome 19, 18069586: 18069586
24 IL12RB1 NM_005535.2(IL12RB1): c.1149C> T (p.Cys383=) single nucleotide variant Conflicting interpretations of pathogenicity rs17882216 GRCh37 Chromosome 19, 18180396: 18180396
25 IL12RB1 NM_005535.2(IL12RB1): c.783+10C> T single nucleotide variant Conflicting interpretations of pathogenicity rs79972275 GRCh38 Chromosome 19, 18073507: 18073507
26 IL12RB1 NM_005535.2(IL12RB1): c.783+10C> T single nucleotide variant Conflicting interpretations of pathogenicity rs79972275 GRCh37 Chromosome 19, 18184317: 18184317
27 IL12RB1 NM_005535.2(IL12RB1): c.271G> A (p.Ala91Thr) single nucleotide variant Benign/Likely benign rs147215816 GRCh37 Chromosome 19, 18191780: 18191780
28 IL12RB1 NM_005535.2(IL12RB1): c.271G> A (p.Ala91Thr) single nucleotide variant Benign/Likely benign rs147215816 GRCh38 Chromosome 19, 18080970: 18080970
29 IL12RB1 NM_005535.2(IL12RB1): c.139C> T (p.Pro47Ser) single nucleotide variant Benign/Likely benign rs17887176 GRCh38 Chromosome 19, 18082250: 18082250
30 IL12RB1 NM_005535.2(IL12RB1): c.139C> T (p.Pro47Ser) single nucleotide variant Benign/Likely benign rs17887176 GRCh37 Chromosome 19, 18193060: 18193060
31 IL12RB1 NM_005535.2(IL12RB1): c.1879G> A (p.Glu627Lys) single nucleotide variant Conflicting interpretations of pathogenicity rs143367415 GRCh37 Chromosome 19, 18170808: 18170808
32 IL12RB1 NM_005535.2(IL12RB1): c.1879G> A (p.Glu627Lys) single nucleotide variant Conflicting interpretations of pathogenicity rs143367415 GRCh38 Chromosome 19, 18059998: 18059998
33 IL12RB1 NM_005535.2(IL12RB1): c.222C> G (p.Ser74Arg) single nucleotide variant Likely benign rs11575925 GRCh37 Chromosome 19, 18192977: 18192977
34 IL12RB1 NM_005535.2(IL12RB1): c.222C> G (p.Ser74Arg) single nucleotide variant Likely benign rs11575925 GRCh38 Chromosome 19, 18082167: 18082167
35 IL12RB1 NM_005535.2(IL12RB1): c.1295C> T (p.Thr432Met) single nucleotide variant Uncertain significance rs200875188 GRCh38 Chromosome 19, 18068421: 18068421
36 IL12RB1 NM_005535.2(IL12RB1): c.1295C> T (p.Thr432Met) single nucleotide variant Uncertain significance rs200875188 GRCh37 Chromosome 19, 18179231: 18179231
37 IL12RB1 NM_005535.2(IL12RB1): c.1172C> T (p.Pro391Leu) single nucleotide variant Uncertain significance rs140254802 GRCh38 Chromosome 19, 18069563: 18069563
38 IL12RB1 NM_005535.2(IL12RB1): c.1172C> T (p.Pro391Leu) single nucleotide variant Uncertain significance rs140254802 GRCh37 Chromosome 19, 18180373: 18180373
39 IL12RB1 NM_005535.2(IL12RB1): c.815A> G (p.Gln272Arg) single nucleotide variant Uncertain significance GRCh37 Chromosome 19, 18183128: 18183128
40 IL12RB1 NM_005535.2(IL12RB1): c.815A> G (p.Gln272Arg) single nucleotide variant Uncertain significance GRCh38 Chromosome 19, 18072318: 18072318
41 IL12RB1 NM_005535.2(IL12RB1): c.102G> A (p.Pro34=) single nucleotide variant Benign rs146978336 GRCh37 Chromosome 19, 18194264: 18194264
42 IL12RB1 NM_005535.2(IL12RB1): c.102G> A (p.Pro34=) single nucleotide variant Benign rs146978336 GRCh38 Chromosome 19, 18083454: 18083454
43 IL12RB1 NM_005535.2(IL12RB1): c.1242C> T (p.Tyr414=) single nucleotide variant Benign rs376271 GRCh37 Chromosome 19, 18179284: 18179284
44 IL12RB1 NM_005535.2(IL12RB1): c.1242C> T (p.Tyr414=) single nucleotide variant Benign rs376271 GRCh38 Chromosome 19, 18068474: 18068474
45 IL12RB1 NM_005535.2(IL12RB1): c.848G> A (p.Arg283Gln) single nucleotide variant Benign rs117511121 GRCh37 Chromosome 19, 18183095: 18183095
46 IL12RB1 NM_005535.2(IL12RB1): c.848G> A (p.Arg283Gln) single nucleotide variant Benign rs117511121 GRCh38 Chromosome 19, 18072285: 18072285
47 IL12RB1 NM_005535.2(IL12RB1): c.1813G> T (p.Val605Leu) single nucleotide variant Likely benign rs145590794 GRCh38 Chromosome 19, 18060064: 18060064
48 IL12RB1 NM_005535.2(IL12RB1): c.1813G> T (p.Val605Leu) single nucleotide variant Likely benign rs145590794 GRCh37 Chromosome 19, 18170874: 18170874
49 IL12RB1 NM_005535.2(IL12RB1): c.772C> G (p.Leu258Val) single nucleotide variant Uncertain significance rs138189707 GRCh37 Chromosome 19, 18184338: 18184338
50 IL12RB1 NM_005535.2(IL12RB1): c.772C> G (p.Leu258Val) single nucleotide variant Uncertain significance rs138189707 GRCh38 Chromosome 19, 18073528: 18073528

Expression for Immunodeficiency 30

Search GEO for disease gene expression data for Immunodeficiency 30.

Pathways for Immunodeficiency 30

GO Terms for Immunodeficiency 30

Sources for Immunodeficiency 30

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74 UMLS via Orphanet
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