title: Alterations of the IKBKG locus and diseases: an update and a report of 13 novel mutations.
abstract: Mutations in the inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma (IKBKG), also called nuclear factor-kappaB (NF-kB) essential modulator (NEMO), gene are the most common single cause of incontinentia pigmenti (IP) in females and anhydrotic ectodermal dysplasia with immunodeficiency (EDA-ID) in males. The IKBKG gene, located in the Xq28 chromosomal region, encodes for the regulatory subunit of the inhibitor of kappaB (IkB) kinase (IKK) complex required for the activation of the NF-kB pathway. Therefore, the remarkably heterogeneous and often severe clinical presentation reported in IP is due to the pleiotropic role of this signaling transcription pathway. A recurrent exon 4_10 genomic rearrangement in the IKBKG gene accounts for 60 to 80% of IP-causing mutations. Besides the IKBKG rearrangement found in IP females (which is lethal in males), a total of 69 different small mutations (missense, frameshift, nonsense, and splice-site mutations) have been reported, including 13 novel ones in this work. The updated distribution of all the IP- and EDA-ID-causing mutations along the IKBKG gene highlights a secondary hotspot mutation in exon 10, which contains only 11% of the protein. Furthermore, familial inheritance analysis revealed an unexpectedly high incidence of sporadic cases (>65%). The sum of the observations can aid both in determining the molecular basis of IP and EDA-ID allelic diseases, and in genetic counseling in affected families.
authors: Institute of Genetics and Biophysics Adriano Buzzati-Traverso (IGB-CNR), Naples, Italy.
authors: Francesca
authors: F
authors: Fusco
authors: Alessandra
authors: A
authors: Pescatore
authors: Elodie
authors: E
authors: Bal
authors: Aida
authors: A
authors: Ghoul
authors: Mariateresa
authors: M
authors: Paciolla
authors: Maria Brigida
authors: MB
authors: Lioi
authors: Michele
authors: M
authors: D'Urso
authors: Smail Hadj
authors: SH
authors: Rabia
authors: Christine
authors: C
authors: Bodemer
authors: Jean Paul
authors: JP
authors: Bonnefont
authors: Arnold
authors: A
authors: Munnich
authors: Maria Giuseppina
authors: MG
authors: Miano
authors: Asma
authors: A
authors: Smahi
authors: Matilde Valeria
authors: MV
authors: Ursini
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D041321:Chromosomes, Human, X; D004247:DNA; D004476:Ectodermal Dysplasia / Q000235:genetics; D005260:Female; D006801:Humans; D051550:I-kappa B Kinase / Q000737:chemistry / Q000235:genetics*; D007184:Incontinentia Pigmenti / Q000235:genetics; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009030:Mosaicism; D009154:Mutation; D017386:Sequence Homology, Amino Acid
chemical_list: C491731:IKBKG protein, human; D004247:DNA; D051550:I-kappa B Kinase