IRAK4 and NEMO mutations in otherwise healthy children with recurrent invasive pneumococcal disease

Cheng Lung Ku, Capucine Picard, Melinda Erdõs, Axel Jeurissen, Jacinta Bustamante, Anne Puel, Horst Von Bernuth, Orchidée Filipe-Santos, Huey Hsuan Chang, Tatiana Lawrence, Marc Raes, László Maródi, Xavier Bossuyt, Jean Laurent Casanova

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111 Citations (Scopus)


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 interteukin (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.

Original languageEnglish
Pages (from-to)16-23
Number of pages8
JournalJournal of medical genetics
Issue number1
Publication statusPublished - Jan 1 2007


ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Ku, C. L., Picard, C., Erdõs, M., Jeurissen, A., Bustamante, J., Puel, A., Von Bernuth, H., Filipe-Santos, O., Chang, H. H., Lawrence, T., Raes, M., Maródi, L., Bossuyt, X., & Casanova, J. L. (2007). IRAK4 and NEMO mutations in otherwise healthy children with recurrent invasive pneumococcal disease. Journal of medical genetics, 44(1), 16-23.