EDA-ID and IP, two faces of the same coin: how the same IKBKG/NEMO mutation affecting the NF-κB pathway can cause immunodeficiency and/or inflammation.

Autor: Fusco F; a Institute of Genetics and Biophysics 'Adriano Buzzati-Traverso' , IGB-CNR, Naples , Italy., Pescatore A; a Institute of Genetics and Biophysics 'Adriano Buzzati-Traverso' , IGB-CNR, Naples , Italy., Conte MI; a Institute of Genetics and Biophysics 'Adriano Buzzati-Traverso' , IGB-CNR, Naples , Italy., Mirabelli P; b Fondazione SDN IRCCS , Naples , Italy., Paciolla M; a Institute of Genetics and Biophysics 'Adriano Buzzati-Traverso' , IGB-CNR, Naples , Italy.; c University of Basilicata , Potenza , Italy., Esposito E; a Institute of Genetics and Biophysics 'Adriano Buzzati-Traverso' , IGB-CNR, Naples , Italy., Lioi MB; c University of Basilicata , Potenza , Italy., Ursini MV; a Institute of Genetics and Biophysics 'Adriano Buzzati-Traverso' , IGB-CNR, Naples , Italy.; b Fondazione SDN IRCCS , Naples , Italy.
Jazyk: angličtina
Zdroj: International reviews of immunology [Int Rev Immunol] 2015; Vol. 34 (6), pp. 445-59. Date of Electronic Publication: 2015 Aug 13.
DOI: 10.3109/08830185.2015.1055331
Abstrakt: Anhidrotic Ectodermal Dysplasia with ImmunoDeficiency (EDA-ID, OMIM 300291) and Incontinentia Pigmenti (IP, OMIM 308300) are two rare diseases, caused by mutations of the IKBKG/NEMO gene. The protein NEMO/IKKγ is essential for the NF-κB activation pathway, involved in a variety of physiological and cellular processes, such as immunity, inflammation, cell proliferation, and survival. A wide spectrum of IKBKG/NEMO mutations have been identified so far, and, on the basis of their effect on NF-κB activation, they are considered hypomorphic or amorphic (loss of function) mutations. IKBKG/NEMO hypomorphic mutations, reducing but not abolishing NF-κB activation, have been identified in EDA-ID and IP patients. Instead, the amorphic mutations, abolishing NF-κB activation by complete IKBKG/NEMO gene silencing, cause only IP. Here, we present an overview of IKBKG/NEMO mutations in EDA-ID and IP patients and describe similarities and differences between the clinical/immunophenotypic and genetic aspects, highlighting any T and B lymphocyte defect, and paying particular attention to the cellular and molecular defects that underlie the pathogenesis of both diseases.
Databáze: MEDLINE
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