#614890
Table of Contents
A number sign (#) is used with this entry because immunodeficiency-29 (IMD29) is caused by homozygous mutation in the IL12B gene (161561) on chromosome 5q33.3.
IMD29 results from autosomal recessive IL12B deficiency and is characterized by undetectable IL12B secretion from leukocytes. IL12B-deficient patients generally present with bacillus Calmette-Guerin (BCG) disease after vaccination in childhood, and at least half also have Salmonella infection. Infections with Mycobacterium tuberculosis and environmental mycobacteria have also been reported in IL12B-deficient patients. The phenotype is relatively mild, and patients have a good prognosis (review by Al-Muhsen and Casanova, 2008).
Altare et al. (1998) described IL12 deficiency in a child with curable BCG and Salmonella enteritidis infection. The girl was born to consanguineous Pakistani parents and received BCG immunization at birth. She presented 3 months later with local ulceration of her immunization site on her left deltoid region, regional lymphadenopathy, and a discharging sinus from which M. bovis BCG was isolated.
Picard et al. (2002) reported 12 additional patients with IL12B deficiency from 5 additional kindreds and reviewed the phenotype of all patients. Among 13 patients with IL12 deficiency, including the patient originally reported by Altare et al. (1998), 1 child had salmonellosis only and 12 suffered from clinical disease due to BCG or environmental nontuberculous mycobacteria. One patient also had clinical disease caused by virulent Mycobacterium tuberculosis, 5 patients had clinical disease caused by Salmonella serotypes, and 1 patient had clinical disease caused by Nocardia asteroides. The clinical outcome varied from case to case. Five patients, aged 2 to 11 years, died of overwhelming infection, whereas 8 patients, aged 3 to 12 years, were still in good health and not taking antibiotics at the time of report.
In the child they reported with curable BCG and Salmonella enteritidis infection, Altare et al. (1998) found a large homozygous deletion (161561.0001) in the IL12B gene precluded expression of functional IL12-p70 cytokine by activated dendritic cells and phagocytes. As a result, interferon-gamma production by lymphocytes was markedly impaired. This was said to be the first discovered human disease caused by a cytokine gene defect, suggesting that IL12 is essential to and appears specific for protective immunity to intracellular bacteria, such as mycobacteria and salmonella.
In 1 kindred in India, Picard et al. (2002) identified the same large deletion in IL12B that was described by Altare et al. (1998) in a Pakistani child. In 4 kindreds in Saudi Arabia, Picard et al. (2002) found a recessive loss-of-function frameshift insertion in IL12B (161561.0002). A conserved haplotype encompassing the IL12B gene suggested that a founder effect accounted for the recurrence of each mutation. The 2 founder mutational events, the deletion and the insertion, were estimated to have occurred approximately 700 and 1,100 years ago, respectively.
Al-Muhsen, S., Casanova, J.-L. The genetic heterogeneity of mendelian susceptibility to mycobacterial diseases. J. Allergy Clin. Immun. 122: 1043-1051, 2008. [PubMed: 19084105, related citations] [Full Text]
Altare, F., Lammas, D., Revy, P., Jouanguy, E., Doffinger, R., Lamhamedi, S., Drysdale, P., Scheel-Toellner, D., Girdlestone, J., Darbyshire, P., Wadhwa, M., Dockrell, H., Salmon, M., Fischer, A., Durandy, A., Casanova, J.-L., Kumararatne, D. S. Inherited interleukin 12 deficiency in a child with bacille Calmette-Guerin and Salmonella enteritidis disseminated infection. J. Clin. Invest. 102: 2035-2040, 1998. [PubMed: 9854038, related citations] [Full Text]
Picard, C., Fieschi, C., Altare, F., Al-Jumaah, S., Al-Hajjar, S., Feinberg, J., Dupuis, S., Soudais, C., Al-Mohsen, I. Z., Genin, E., Lammas, D., Kumararatne, D. S., and 12 others. Inherited interleukin-12 deficiency: IL12B genotype and clinical phenotype of 13 patients from six kindreds. Am. J. Hum. Genet. 70: 336-348, 2002. [PubMed: 11753820, images, related citations] [Full Text]
Alternative titles; symbols
ORPHA: 319558; DO: 0111950;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 5q33.3 | Immunodeficiency 29, mycobacteriosis | 614890 | Autosomal recessive | 3 | IL12B | 161561 |
A number sign (#) is used with this entry because immunodeficiency-29 (IMD29) is caused by homozygous mutation in the IL12B gene (161561) on chromosome 5q33.3.
IMD29 results from autosomal recessive IL12B deficiency and is characterized by undetectable IL12B secretion from leukocytes. IL12B-deficient patients generally present with bacillus Calmette-Guerin (BCG) disease after vaccination in childhood, and at least half also have Salmonella infection. Infections with Mycobacterium tuberculosis and environmental mycobacteria have also been reported in IL12B-deficient patients. The phenotype is relatively mild, and patients have a good prognosis (review by Al-Muhsen and Casanova, 2008).
Altare et al. (1998) described IL12 deficiency in a child with curable BCG and Salmonella enteritidis infection. The girl was born to consanguineous Pakistani parents and received BCG immunization at birth. She presented 3 months later with local ulceration of her immunization site on her left deltoid region, regional lymphadenopathy, and a discharging sinus from which M. bovis BCG was isolated.
Picard et al. (2002) reported 12 additional patients with IL12B deficiency from 5 additional kindreds and reviewed the phenotype of all patients. Among 13 patients with IL12 deficiency, including the patient originally reported by Altare et al. (1998), 1 child had salmonellosis only and 12 suffered from clinical disease due to BCG or environmental nontuberculous mycobacteria. One patient also had clinical disease caused by virulent Mycobacterium tuberculosis, 5 patients had clinical disease caused by Salmonella serotypes, and 1 patient had clinical disease caused by Nocardia asteroides. The clinical outcome varied from case to case. Five patients, aged 2 to 11 years, died of overwhelming infection, whereas 8 patients, aged 3 to 12 years, were still in good health and not taking antibiotics at the time of report.
In the child they reported with curable BCG and Salmonella enteritidis infection, Altare et al. (1998) found a large homozygous deletion (161561.0001) in the IL12B gene precluded expression of functional IL12-p70 cytokine by activated dendritic cells and phagocytes. As a result, interferon-gamma production by lymphocytes was markedly impaired. This was said to be the first discovered human disease caused by a cytokine gene defect, suggesting that IL12 is essential to and appears specific for protective immunity to intracellular bacteria, such as mycobacteria and salmonella.
In 1 kindred in India, Picard et al. (2002) identified the same large deletion in IL12B that was described by Altare et al. (1998) in a Pakistani child. In 4 kindreds in Saudi Arabia, Picard et al. (2002) found a recessive loss-of-function frameshift insertion in IL12B (161561.0002). A conserved haplotype encompassing the IL12B gene suggested that a founder effect accounted for the recurrence of each mutation. The 2 founder mutational events, the deletion and the insertion, were estimated to have occurred approximately 700 and 1,100 years ago, respectively.
Al-Muhsen, S., Casanova, J.-L. The genetic heterogeneity of mendelian susceptibility to mycobacterial diseases. J. Allergy Clin. Immun. 122: 1043-1051, 2008. [PubMed: 19084105] [Full Text: https://doi.org/10.1016/j.jaci.2008.10.037]
Altare, F., Lammas, D., Revy, P., Jouanguy, E., Doffinger, R., Lamhamedi, S., Drysdale, P., Scheel-Toellner, D., Girdlestone, J., Darbyshire, P., Wadhwa, M., Dockrell, H., Salmon, M., Fischer, A., Durandy, A., Casanova, J.-L., Kumararatne, D. S. Inherited interleukin 12 deficiency in a child with bacille Calmette-Guerin and Salmonella enteritidis disseminated infection. J. Clin. Invest. 102: 2035-2040, 1998. [PubMed: 9854038] [Full Text: https://doi.org/10.1172/JCI4950]
Picard, C., Fieschi, C., Altare, F., Al-Jumaah, S., Al-Hajjar, S., Feinberg, J., Dupuis, S., Soudais, C., Al-Mohsen, I. Z., Genin, E., Lammas, D., Kumararatne, D. S., and 12 others. Inherited interleukin-12 deficiency: IL12B genotype and clinical phenotype of 13 patients from six kindreds. Am. J. Hum. Genet. 70: 336-348, 2002. [PubMed: 11753820] [Full Text: https://doi.org/10.1086/338625]
Dear OMIM User,
To ensure long-term funding for the OMIM project, we have diversified our revenue stream. We are determined to keep this website freely accessible. Unfortunately, it is not free to produce. Expert curators review the literature and organize it to facilitate your work. Over 90% of the OMIM's operating expenses go to salary support for MD and PhD science writers and biocurators. Please join your colleagues by making a donation now and again in the future. Donations are an important component of our efforts to ensure long-term funding to provide you the information that you need at your fingertips.
Thank you in advance for your generous support,
Ada Hamosh, MD, MPH
Scientific Director, OMIM