http://purl.uniprot.org/citations/18851874 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/18851874 | http://www.w3.org/2000/01/rdf-schema#comment | "BackgroundHuman hypomorphic nuclear factor-kappaB essential modulator (NEMO) mutations cause diverse clinical and immunologic phenotypes, but understanding of their scope and mechanistic links to immune function and genotype is incomplete.ObjectiveWe created and analyzed a database of hypomorphic NEMO mutations to determine the spectrum of phenotypes and their associated genotypes and sought to establish a standardized NEMO reconstitution system to obtain mechanistic insights.MethodsPhenotypes of 72 individuals with NEMO mutations were compiled. NEMO L153R and C417R were investigated further in a reconstitution system. TNF-alpha or Toll-like receptor (TLR)-5 signals were evaluated for nuclear factor-kappaB activation, programmed cell death, and A20 gene expression.ResultsThirty-two different mutations were identified; 53% affect the zinc finger domain. Seventy-seven percent were associated with ectodermal dysplasia, 86% with serious pyogenic infection, 39% with mycobacterial infection, 19% with serious viral infection, and 23% with inflammatory diseases. Thirty-six percent of individuals died at a mean age of 6.4 years. CD40, IL-1, TNF-alpha, TLR, and T-cell receptor signals were impaired in 15 of 16 (94%), 6 of 7 (86%), 9 of 11 (82%), 9 of 14 (64%), and 7 of 18 (39%), respectively. Hypomorphism-reconstituted NEMO-deficient cells demonstrated partial restoration of NEMO functions. Although both L153R and C417R impaired TLR and TNF-alpha-induced NF-kappaB activation, L153R also increased TNF-alpha-induced programmed cell death with decreased A20 expression.ConclusionDistinct NEMO hypomorphs define specific disease and genetic characteristics. A reconstitution system can identify attributes of hypomorphisms independent of an individual's genetic background. Apoptosis susceptibility in L153R reconstituted cells defines a specific phenotype of this mutation that likely contributes to the excessive inflammation with which it is clinically associated."xsd:string |
http://purl.uniprot.org/citations/18851874 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.jaci.2008.08.018"xsd:string |
http://purl.uniprot.org/citations/18851874 | http://purl.uniprot.org/core/author | "May M.J."xsd:string |
http://purl.uniprot.org/citations/18851874 | http://purl.uniprot.org/core/author | "Orange J.S."xsd:string |
http://purl.uniprot.org/citations/18851874 | http://purl.uniprot.org/core/author | "Banerjee P.P."xsd:string |
http://purl.uniprot.org/citations/18851874 | http://purl.uniprot.org/core/author | "Monaco-Shawver L."xsd:string |
http://purl.uniprot.org/citations/18851874 | http://purl.uniprot.org/core/author | "Solt L.A."xsd:string |
http://purl.uniprot.org/citations/18851874 | http://purl.uniprot.org/core/author | "Hanson E.P."xsd:string |
http://purl.uniprot.org/citations/18851874 | http://purl.uniprot.org/core/author | "Madge L.A."xsd:string |
http://purl.uniprot.org/citations/18851874 | http://purl.uniprot.org/core/date | "2008"xsd:gYear |
http://purl.uniprot.org/citations/18851874 | http://purl.uniprot.org/core/name | "J Allergy Clin Immunol"xsd:string |
http://purl.uniprot.org/citations/18851874 | http://purl.uniprot.org/core/pages | "1169-1177.e16"xsd:string |
http://purl.uniprot.org/citations/18851874 | http://purl.uniprot.org/core/title | "Hypomorphic nuclear factor-kappaB essential modulator mutation database and reconstitution system identifies phenotypic and immunologic diversity."xsd:string |
http://purl.uniprot.org/citations/18851874 | http://purl.uniprot.org/core/volume | "122"xsd:string |
http://purl.uniprot.org/citations/18851874 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/18851874 |
http://purl.uniprot.org/citations/18851874 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/18851874 |
http://purl.uniprot.org/uniprot/#_A0A087X1B1-mappedCitation-18851874 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18851874 |
http://purl.uniprot.org/uniprot/#_D3DWY0-mappedCitation-18851874 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18851874 |
http://purl.uniprot.org/uniprot/#_Q9Y6K9-mappedCitation-18851874 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18851874 |
http://purl.uniprot.org/uniprot/Q9Y6K9 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/18851874 |
http://purl.uniprot.org/uniprot/D3DWY0 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/18851874 |
http://purl.uniprot.org/uniprot/A0A087X1B1 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/18851874 |