Novel hypomorphic mutation in IKBKG impairs NEMO-ubiquitylation causing ectodermal dysplasia, immunodeficiency, incontinentia pigmenti, and immune thrombocytopenic purpura
| Autor: | Paola Valenzuela-León, Carola Duran-McKinster, Marco Antonio Yamazaki-Nakashimada, Francisco Rivas-Larrauri, Leopoldo Santos-Argumedo, Noé Ramírez-Alejo, Julio C. Alcántara-Montiel, Rosaura Hernández-Rivas, Leticia Cedillo-Barrón |
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| Rok vydání: | 2015 |
| Předmět: |
Adult
Male congenital hereditary and neonatal diseases and abnormalities Ectodermal dysplasia Heterozygote Adolescent Immunology Mutation Missense Biology medicine.disease_cause chemistry.chemical_compound Ectodermal Dysplasia IKBKG medicine Immunology and Allergy Missense mutation Humans Family Incontinentia Pigmenti skin and connective tissue diseases Immunodeficiency Mutation Purpura Thrombocytopenic Idiopathic Immunologic Deficiency Syndromes Ubiquitination NF-κB Incontinentia pigmenti medicine.disease Thrombocytopenic purpura I-kappa B Kinase chemistry Female |
| Zdroj: | Clinical immunology (Orlando, Fla.). 160(2) |
| ISSN: | 1521-7035 |
| Popis: | NF-κB essential modulator (NEMO) is a component of the IKK complex, which participates in the activation of the NF-κB pathway. Hypomorphic mutations in the IKBKG gene result in different forms of anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) in males without affecting carrier females. Here, we describe a hypomorphic and missense mutation, designated c.916G>A (p.D306N), which affects our patient, his mother, and his sister. This mutation did not affect NEMO expression; however, an immunoprecipitation assay revealed reduced ubiquitylation upon CD40-stimulation in the patient's cells. Functional studies have demonstrated reduced phosphorylation and degradation of IκBα, affecting NF-κB recruitment into the nucleus. The patient presented with clinical features of ectodermal dysplasia, immunodeficiency, and immune thrombocytopenic purpura, the latter of which has not been previously reported in a patient with NEMO deficiency. His mother and sister displayed incontinentia pigmenti indicating that, in addition to amorphic mutations, hypomorphic mutations in NEMO can affect females. |
| Databáze: | OpenAIRE |
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