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http://purl.uniprot.org/citations/15356572http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/15356572http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/15356572http://www.w3.org/2000/01/rdf-schema#comment"

Background

Many receptors rely on the appropriate activation of nuclear factor (NF) kappa B to induce cellular function. This process depends critically on the phosphorylation of the inhibitor of NF-kappa B (I kappa B) by the I kappa B kinase. This targets I kappa B for ubiquitination and degradation, allowing NF-kappa B to translocate to the nucleus, where it can direct transcription. Hypomorphic human mutations affecting one I kappa B kinase component, the NF-kappa B essential modulator (NEMO), result in impaired signaling from receptors required for ectodermal development and immune function. Male subjects with these mutant NEMO molecules have an X-linked syndrome known as ectodermal dysplasia with immunodeficiency, which is characterized by severe infections, with herpesviruses, bacteria, and mycobacterial susceptibility.

Objective

We sought to genetically and biochemically characterize a patient with a mutant NEMO molecule without ectodermal abnormalities.

Methods

We evaluated NEMO in a patient who had immunodeficiency and atypical mycobacterial infection but normal ectoderm.

Results

We identified a novel NEMO mutant causing immunodeficiency without ectodermal dysplasia. The mutation, which altered the exon 9 splice site, was present in cells of ectodermal and hematopoetic origin and resulted in a heterogeneous mixture of mutant and wild-type cDNA species. Immunologic function was variably impaired, with reduced CD40-induced B-cell proliferation, partially reduced NF-kappa B p65 nuclear translocation, and variable Toll-like receptor-induced TNF production. This variability might be explained by an inconsistent ratio of mutant to wild-type NEMO. The lack of any ectodermal phenotype, however, suggested a separation in the hematopoetic and ectodermal function of NEMO that leads to NF-kappa B activation.

Conclusion

Mutation of the gene encoding NEMO can result in immunodeficiency without ectodermal dysplasia."xsd:string
http://purl.uniprot.org/citations/15356572http://purl.org/dc/terms/identifier"doi:10.1016/j.jaci.2004.06.052"xsd:string
http://purl.uniprot.org/citations/15356572http://purl.org/dc/terms/identifier"doi:10.1016/j.jaci.2004.06.052"xsd:string
http://purl.uniprot.org/citations/15356572http://purl.uniprot.org/core/author"Roy R.M."xsd:string
http://purl.uniprot.org/citations/15356572http://purl.uniprot.org/core/author"Roy R.M."xsd:string
http://purl.uniprot.org/citations/15356572http://purl.uniprot.org/core/author"Fleisher T.A."xsd:string
http://purl.uniprot.org/citations/15356572http://purl.uniprot.org/core/author"Fleisher T.A."xsd:string
http://purl.uniprot.org/citations/15356572http://purl.uniprot.org/core/author"Orange J.S."xsd:string
http://purl.uniprot.org/citations/15356572http://purl.uniprot.org/core/author"Orange J.S."xsd:string
http://purl.uniprot.org/citations/15356572http://purl.uniprot.org/core/author"Levy O."xsd:string
http://purl.uniprot.org/citations/15356572http://purl.uniprot.org/core/author"Levy O."xsd:string
http://purl.uniprot.org/citations/15356572http://purl.uniprot.org/core/author"Krzewski K."xsd:string
http://purl.uniprot.org/citations/15356572http://purl.uniprot.org/core/author"Krzewski K."xsd:string
http://purl.uniprot.org/citations/15356572http://purl.uniprot.org/core/author"Geha R.S."xsd:string
http://purl.uniprot.org/citations/15356572http://purl.uniprot.org/core/author"Geha R.S."xsd:string
http://purl.uniprot.org/citations/15356572http://purl.uniprot.org/core/author"Niemela J.E."xsd:string
http://purl.uniprot.org/citations/15356572http://purl.uniprot.org/core/author"Niemela J.E."xsd:string
http://purl.uniprot.org/citations/15356572http://purl.uniprot.org/core/author"Bonilla F.A."xsd:string
http://purl.uniprot.org/citations/15356572http://purl.uniprot.org/core/author"Bonilla F.A."xsd:string
http://purl.uniprot.org/citations/15356572http://purl.uniprot.org/core/author"Brodeur S.R."xsd:string
http://purl.uniprot.org/citations/15356572http://purl.uniprot.org/core/author"Brodeur S.R."xsd:string
http://purl.uniprot.org/citations/15356572http://purl.uniprot.org/core/date"2004"xsd:gYear
http://purl.uniprot.org/citations/15356572http://purl.uniprot.org/core/date"2004"xsd:gYear
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