TY - JOUR
T1 - EDA-ID and IP, Two Faces of the Same Coin
T2 - How the Same IKBKG / NEMO Mutation Affecting the NF-B Pathway Can Cause Immunodeficiency and/or Inflammation
AU - Fusco, Francesca
AU - Pescatore, Alessandra
AU - Conte, Matilde Immacolata
AU - Mirabelli, Peppino
AU - Paciolla, Mariateresa
AU - Esposito, Elio
AU - Lioi, Maria Brigida
AU - Ursini, Matilde Valeria
PY - 2015/11/2
Y1 - 2015/11/2
N2 - 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-B 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-B activation, they are considered hypomorphic or amorphic (loss of function) mutations. IKBKG/NEMO hypomorphic mutations, reducing but not abolishing NF-B activation, have been identified in EDA-ID and IP patients. Instead, the amorphic mutations, abolishing NF-B 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.
AB - 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-B 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-B activation, they are considered hypomorphic or amorphic (loss of function) mutations. IKBKG/NEMO hypomorphic mutations, reducing but not abolishing NF-B activation, have been identified in EDA-ID and IP patients. Instead, the amorphic mutations, abolishing NF-B 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.
KW - IKBKG/NEMO mutations
KW - immunodeficiency
KW - inflammation
KW - mutation sequence analysis
KW - NF-κB
UR - http://www.scopus.com/inward/record.url?scp=84947027239&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84947027239&partnerID=8YFLogxK
U2 - 10.3109/08830185.2015.1055331
DO - 10.3109/08830185.2015.1055331
M3 - Article
C2 - 26269396
AN - SCOPUS:84947027239
VL - 34
SP - 445
EP - 459
JO - International Reviews of Immunology
JF - International Reviews of Immunology
SN - 0883-0185
IS - 6
ER -