The range of defects associated with nuclear factor κB essential modulator

Current Opinion in Allergy and Clinical Immunology

Volumn 5, Issue 6, 2005, Pages 513-518

  Uzel, Gulbu ^a,b  

^a NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES   (United States)

^b Laboratory of Clinical Infectious Diseases   (United States)

Author keywords

Ectodermal dysplasia; Immunodeficiency; NEMO; NF B; Nonpathogenic mycobacterial infection; Nuclear factor; Nuclear factor B essential modulator

Indexed keywords

I KAPPA B; I KAPPA B KINASE GAMMA; PROTEIN; TOLL LIKE RECEPTOR; UNCLASSIFIED DRUG;

ALBERS SCHOENBERG DISEASE; ARTICLE; AUTOSOMAL DOMINANT INHERITANCE; BACTERIAL INFECTION; ECTODERMAL DYSPLASIA; GENE FUNCTION; GENOTYPE PHENOTYPE CORRELATION; HUMAN; HYPERIMMUNOGLOBULINEMIA M; IMMUNE DEFICIENCY; IMMUNOPATHOLOGY; INCIDENCE; INCONTINENTIA PIGMENTI; INFECTION SENSITIVITY; LYMPHEDEMA; NONHUMAN; POINT MUTATION; PRIORITY JOURNAL; PROTEIN DEFECT; RECESSIVE INHERITANCE; REGULATORY MECHANISM; VIRUS INFECTION; X CHROMOSOME LINKED DISORDER;

EID: 27944501076     PISSN: 15284050     EISSN: 14736322     Source Type: Journal    
DOI: 10.1097/01.all.0000191241.66373.74     Document Type: Article

References (33)

1. Courtois G, Smahi A, Israel A. NEMO/IKK gamma: linking NF-kappa B to human disease. Trends Mol Med 2001; 7:427-430.
2. Smahi A, Courtois G, Rabia SH, et al. The NF-kappaB signalling pathway in human diseases: from incontinentia pigmenti to ectodermal dysplasias and immune-deficiency syndromes. Hum Mol Genet 2002; 11:2371-2375.
3. Baeuerle PA, Baltimore D. Activation of DNA-binding activity in an apparently cytoplasmic precursor of the NF-kappa B transcription factor. Cell 1988; 53:211-217.
4. Hoffmann A, Leung TH, Baltimore D. Genetic analysis of NF-kappaB/Rel transcription factors defines functional specificities. EMBO J 2003; 22:5530-5539.
5. Orange JS, Levy O, Geha RS. Human disease resulting from gene mutations that interfere with appropriate nuclear factor-kappaB activation. Immunol Rev 2005; 203:21-37. This review discusses how genetic defects are linked to inappropriate activation of NFκB and result in discrete disease entities. This paper is also a concise review of cell-signaling pathways that rely upon NFκB activation.
6. Karin M, Ben-Neriah Y. Phosphorylation meets ubiquitination: the control of NF-[kappa]B activity. Annu Rev Immunol 2000; 18:621-663.
7. Israel A. The IKK complex: an integrator of all signals that activate NF-kappaB? Trends Cell Biol 2000; 10:129-133.
8. Rothwarf DM, Zandi E, Natoli G, Karin M. IKK-gamma is an essential regulatory subunit of the IkappaB kinase complex. Nature 1998; 395:297-300.
9. Schmidt-Supprian M, Bloch W, Courtois G, et al. NEMO/IKK gamma-deficient mice model incontinentia pigmenti. Mol Cell 2000; 5:981-992.
10. Makris C, Godfrey VL, Krahn-Senftleben G, et al. Female mice heterozygous for IKK gamma/NEMO deficiencies develop a dermatopathy similar to the human X-linked disorder incontinentia pigmenti. Mol Cell 2000; 5:969-979.
11. Courtois G, Israel A. NF-kappa B defects in humans: the NEMO/incontinentia pigmenti connection. Sci STKE 2000; 2000(58):PE1.
12. Zonana J, Elder ME, Schneider LC, et al. A novel X-linked disorder of immune deficiency and hypohidrotic ectodermal dysplasia is allelic to incontinentia pigmenti and due to mutations in IKK-gamma (NEMO). Am J Hum Genet 2000; 67:1555-1562.
13. Doffinger R, Smahi A, Bessia C, et al. X-linked anhidrotic ectodermal dysplasia with immunodeficiency is caused by impaired NF-kappaB signaling. Nat Genet 2001; 27:277-285.
14. Jain A, Ma CA, Lopez-Granados E, et al. Specific NEMO mutations impair CD40-mediated c-Rel activation and B cell terminal differentiation. J Clin Invest 2004; 114:1593-1602.
15. Jain A, Ma CA, Liu S, et al. Specific missense mutations in NEMO result in hyper-IgM syndrome with hypohydrotic ectodermal dysplasia. Nat Immunol 2001; 2:223-228.
16. Orange JS, Jain A, Ballas ZK, et al. The presentation and natural history of immunodeficiency caused by nuclear factor kappaB essential modulator mutation. J Allergy Clin Immunol 2004; 113:725-733.
17. Orange JS, Levy O, Brodeur SR, et al. Human nuclear factor kappa B essential modulator mutation can result in immunodeficiency without ectodermal dysplasia. J Allergy Clin Immunol 2004; 114:650-656. Orange et al. describe a patient with a novel NEMO mutation and no ectodermal abnormalities. They characterize this patient genetically and biochemically and draw attention to the fact that there is a separation in the hematopoietic and ectodermal function of NEMO that leads to NFκB activation.
18. Puel A, Picard C, Ku CL, et al. Inherited disorders of NF-kappaB-mediated immunity in man. Curr Opin Immunol 2004; 16:34-41.
19. Etzioni A, Ochs HD. The hyper IgM syndrome - an evolving story. Pediatr Res 2004; 56:519-525.
20. Ottenhoff TH, Verreck FA, Hoeve MA, van de Vosse E. Control of human host immunity to mycobacteria. Tuberculosis (Edinb) 2005; 85:53-64. This review discusses host defense that plays a critical role in controlling susceptibility to intracellular pathogens and the genetics involving these factors.
21. Dai YS, Liang MG, Gellis SE, et al. Characteristics of mycobacterial infection in patients with immunodeficiency and nuclear factor-kappaB essential modulator mutation, with or without ectodermal dysplasia. J Am Acad Dermatol 2004; 51:718-722.
22. Rosenzweig SD, Holland SM. Congenital defects in the interferon-gamma/ interleukin-12 pathway. Curr Opin Pediatr 2004; 16:3-8.
23. Niehues T, Reichenbach J, Neubert J, et al. Nuclear factor kappaB essential modulator-deficient child with immunodeficiency yet without anhidrotic ectodermal dysplasia. J Allergy Clin Immunol 2004; 114:1456-1462.
24. Orange JS, Brodeur SR, Jain A, et al. Deficient natural killer cell cytotoxicity in patients with IKK-gamma/NEMO mutations. J Clin Invest 2002; 109:1501-1509.
25. Nishikomori R, Akutagawa H, Maruyama K, et al. X-linked ectodermal dysplasia and immunodeficiency caused by reversion mosaicism of NEMO reveals a critical role for NEMO in human T-cell development and/or survival. Blood 2004; 103:4565-4572.
26. Holmstrom G, Bergendal B, Hallberg G, et al. Incontinentia pigmenti. A rare disease with many symptoms [in Swedish] Lakartidningen 2002; 99:1345-1350.
27. Fusco F, Bardaro T, Fimiani G, et al. Molecular analysis of the genetic defect in a large cohort of IP patients and identification of novel NEMO mutations interfering with NF-kappaB activation. Hum Mol Genet 2004; 13:1763-1773. This paper reports on a large cohort of incontinentia pigmenti patients and evaluates them from the genotype-phenotype correlation standpoint. The authors conclude that pathogenesis and severity of incontinentia pigmenti depends on a combination of X inactivation and the integrity of the protein domain on NEMO that recruits upstream factors and activates NFκB.
28. Smahi A, Courtois G, Vabres P, et al. Genomic rearrangement in NEMO impairs NF-kappaB activation and is a cause of incontinentia pigmenti. The International Incontinentia Pigmenti (IP) Consortium. Nature 2000; 405:466-472.
29. Aradhya S, Woffendin H, Jakins T, et al. A recurrent deletion in the ubiquitously expressed NEMO (IKK-gamma) gene accounts for the vast majority of incontinentia pigmenti mutations. Hum Mol Genet 2001; 10:2171-2179.
30. Aradhya S, Bardaro T, Galgoczy P, et al. Multiple pathogenic and benign genomic rearrangements occur at a 35 kb duplication involving the NEMO and LAGE2 genes. Hum Mol Genet 2001; 10:2557-2567.
31. Parrish JE, Scheuerle AE, Lewis RA, et al. Selection against mutant alleles in blood leukocytes is a consistent feature in Incontinentia Pigmenti type 2. Hum Mol Genet 1996; 5:1777-1783.
32. Courtois G, Smahi A, Reichenbach J, et al. A hypermorphic IkappaBalpha mutation is associated with autosomal dominant anhidrotic ectodermal dysplasia and T cell immunodeficiency. J Clin Invest 2003; 112:1108-1115.
33. Orange JS, Geha RS. Finding NEMO: genetic disorders of NF-[kappa]B activation. J Clin Invest 2003; 112:983-985.