Immunodeficiency and disseminated mycobacterial infection associated with homozygous nonsense mutation of IKKβ

Burns, Siobhan O.; Plagnol, Vincent; Morillo-Gutierrez, Beatriz; Zahrani, Daifulah Al; Curtis, James; Gaspar, Miguel; Hassan, Amel; Jones, Alison; Malone, Marian; Rampling, Dyanne; McLatchie, Alex P.; Döffinger, Rainer; Gilmour, Kimberly; Henriquez, Frances; Thrasher, Adrian J.; Gaspar, H. Bobby; Nejentsev, Sergey

doi:10.1016/j.jaci.2013.12.1093

Cited by 38 publications

(28 citation statements)

References 14 publications

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“…Interestingly, while this manuscript was in preparation/review, 2 other IKBKB mutations in CID patients were reported: one a duplication of exon 13 (IKBKB13Dup), 15 and the other Y107X nonsense mutation of IKBKB. 16 The clinical features of our patients were similar to those in the other 2 reports, with early infections with candida, gram-negative bacteria, viruses, and mycobacteria. The immunological features were also similar: They all have elevated numbers of naive T cells that were poorly activated by antigens and anti-CD3, low numbers of B cells that were also naive, and low numbers and function of NK cells.…”

Section: Discussionsupporting

confidence: 88%

“…15 The effect of IKKb(Y107X) mutation on IKKa and NEMO expression was not reported. 16 sequencing data; H.W. participated in functional studies; M.A.…”

Section: Discussionmentioning

confidence: 99%

“…14 We report a homozygous nonsense mutation in IKBKB in 4 patients with CID from 2 unrelated families and compare and contrast our findings with those in 2 other recent reports of mutations in this gene. 15,16 Patient, materials, and methods Abbreviated information is presented here. Details are provided in the supplemental Data, available on the Blood Web site.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

A nonsense mutation in IKBKB causes combined immunodeficiency

Mousallem

Yang

Urban

et al. 2014

Blood

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Section: Discussionsupporting

confidence: 88%

“…15 The effect of IKKb(Y107X) mutation on IKKa and NEMO expression was not reported. 16 sequencing data; H.W. participated in functional studies; M.A.…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A nonsense mutation in IKBKB causes combined immunodeficiency

Mousallem

Yang

Urban

et al. 2014

Blood

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“…One patients displayed mycobacterial diseases . Homozygous LOF mutations in IKBKB , encoding IKK2, a component of the IKK complex, have also been reported . Patients display hypogammaglobulinemia, an excess of naïve T and B cells and they suffer from bacterial, viral, and fungal infections with or without the clinical signs of EDA.…”

Section: Anhidrotic Ectodermal Dysplasia With Immunodeficiency (Eda‐id)mentioning

confidence: 99%

Inherited and acquired immunodeficiencies underlying tuberculosis in childhood

Boisson–Dupuis

Bustamante

El-Baghdadi

et al. 2015

Immunological Reviews

192

165

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Summary Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb) and a few related mycobacteria, is a devastating disease, killing more than a million individuals per year worldwide. However, its pathogenesis remains largely elusive, as only a small proportion of infected individuals develop clinical disease either during primary infection or during reactivation from latency or secondary infection. Subacute, hematogenous, and extrapulmonary disease tends to be more frequent in infants, children, and teenagers than in adults. Life-threatening primary TB of childhood can result from known acquired or inherited immunodeficiencies, although the vast majority of cases remain unexplained. We review here the conditions conferring a predisposition to childhood clinical diseases caused by mycobacteria, including not only M.tb but also weakly virulent mycobacteria, such as BCG vaccines and environmental mycobacteria. Infections with weakly virulent mycobacteria are much rarer than TB, but the inherited and acquired immunodeficiencies underlying these infections are much better known. Their study has also provided genetic and immunological insights into childhood TB, as illustrated by the discovery of single-gene inborn errors of IFN-γ immunity underlying severe cases of TB. Novel findings are expected from ongoing and future human genetic studies of childhood TB in countries that combine a high proportion of consanguineous marriages, a high incidence of TB, and an excellent clinical care, such as Iran, Morocco, and Turkey.

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“…Clinical presentation resembles both IκBα and NEMO mutations (3). Affected patients present in infancy with life-threatening bacterial, fungal, and viral infections and failure to thrive.…”

Section: Discussionmentioning

confidence: 99%

IRAK4 Deficiency in a Patient with Recurrent Pneumococcal Infections: Case Report and Review of the Literature

et al. 2017

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Primary immunodeficiencies are genetic defects of the innate or adaptive immune system, resulting in a propensity to infections. The innate immune system is the first line of defense against pathogens and is critical to recognize microbes and start the inflammatory cascade. Sensing of microbes occurs by a number of pathogen-recognition receptors, resulting in the activation of inflammatory signal transduction pathways, such as the activation of NF-κB. Herein, we describe a case of IRAK4 deficiency, a key signal transduction molecule of toll-like and IL-1 receptors. We highlight the complexities in diagnosis of these disorders and review genetic defects of the NF-κB pathway.

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Immunodeficiency and disseminated mycobacterial infection associated with homozygous nonsense mutation of IKKβ

Cited by 38 publications

References 14 publications

A nonsense mutation in IKBKB causes combined immunodeficiency

A nonsense mutation in IKBKB causes combined immunodeficiency

Inherited and acquired immunodeficiencies underlying tuberculosis in childhood

IRAK4 Deficiency in a Patient with Recurrent Pneumococcal Infections: Case Report and Review of the Literature

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