Journal of medical genetics, 2007-01, Vol.44 (1), p.16-23
2007
Details
- Autor(en) / Beteiligte
- Titel
- IRAK4 and NEMO mutations in otherwise healthy children with recurrent invasive pneumococcal disease
- Ist Teil von
- Journal of medical genetics, 2007-01, Vol.44 (1), p.16-23
- Ort / Verlag
- London: BMJ Publishing Group Ltd
- Erscheinungsjahr
- 2007
- Link zum Volltext
- Quelle
- BMJ Journals Archiv - DFG Nationallizenzen
- Beschreibungen/Notizen
- Background: About 2% of childhood episodes of invasive pneumococcal disease (IPD) are recurrent, and most remain unexplained. Objective: To report two cases of otherwise healthy, unrelated children with recurrent IPD as the only clinical infectious manifestation of an inherited disorder in nuclear factor-κB(NF-κB)-dependent immunity. Results: One child carried two germline mutations in IRAK4, and had impaired cellular responses to interleukin (IL)1 receptor and toll-like receptor (TLR) stimulation. The other child carried a hemizygous mutation in NEMO, associated with a broader impairment of NF-κB activation, with an impaired cellular response to IL-1R, TLR and tumour necrosis factor receptor stimulation. The two patients shared a narrow clinical phenotype, associated with two related but different genotypes. Conclusions: Otherwise healthy children with recurrent IPD should be explored for underlying primary immunodeficiencies affecting the IRAK4-dependent and NEMO-dependent signalling pathways.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0022-2593, 1468-6244eISSN: 1468-6244DOI: 10.1136/jmg.2006.044446Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2597905
- Format
- –
- Schlagworte
- Anti-Bacterial Agents - therapeutic use, Antibody Formation, Bacterial diseases, Biological and medical sciences, C reactive protein, Carbohydrates, Ceftriaxone - therapeutic use, Child, Child, Preschool, Congenital diseases, CRP, Defects, DNA, Complementary, ectodermal dysplasia, EDA, Exons, Fundamental and applied biological sciences. Psychology, General aspects. Genetic counseling, Genetics of eukaryotes. Biological and molecular evolution, Genotype & phenotype, HIV, Human bacterial diseases, Human immunodeficiency virus, Humans, I-kappa B Kinase - genetics, I-kappa B Kinase - metabolism, Immunoglobulins, Immunologic Deficiency Syndromes - genetics, Immunology, Infectious diseases, Interleukin-1 - immunology, Interleukin-1 Receptor-Associated Kinases - genetics, Interleukin-1 Receptor-Associated Kinases - metabolism, Introns, invasive pneumococcal disese, IPD, Male, Medical genetics, Medical sciences, Meningitis, Molecular and cellular biology, Mutation, NF-kappa B - immunology, Original, Patients, PCR, PID, PMN, Pneumococcal Infections - drug therapy, Pneumococcal Infections - genetics, Pneumococcal Infections - immunology, Pneumococcal Infections - pathology, Pneumococcal Vaccines - immunology, Pneumonia, Polymerase Chain Reaction, polymorphonuclear neutrophil, primary immunodeficiency, Recurrence, reverse transcription PCR, RT-PCR, Signal Transduction, Staphylococcal infections, streptococcal infections, pneumococcal infections, Streptococcus infections, Streptococcus pneumoniae, Streptococcus pneumoniae - chemistry, Streptococcus pneumoniae - immunology, TLR, TNF, toll like receptor, tumour necrosis factor, Vaccines