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A novel inhibitor of nuclear factor kappa-B kinase subunit gamma mutation identified in an incontinentia pigmenti patient with syndromic tooth agenesis.

Abstract：

OBJECTIVE:To explore the gene mutation in an incontinentia pigmenti (IP) patient with syndromic tooth agenesis. METHODS:Long-range polymerase chain reaction (PCR) and Sanger sequencing were used to detect inhibitor of nuclear factor kappa-B kinase subunit gamma (IKBKG) mutation in the IP patient. We used the nuclear factor kappa B (NF-κB) reporter gene to assess activation of NF-κB, after transfecting an empty vector, wild-type, or mutant NF-κB essential modulator (NEMO) plasmid into IKBKG-deficient HEK293T cells, respectively. Furthermore, we performed immunoprecipitation and immunoblotting to describe the polyubiquitination of NEMO. Lastly, we detected the interactions between mutant NEMO and I kappa B kinase alpha (IKKα), I kappa B kinase beta (IKKβ), TNF receptor associated factor 6 (TRAF6), HOIL-1-interacting protein (HOIP), hemo-oxidized iron regulatory protein 2 ligase 1 (HOIL-1), and SHANK-associated RH domain interactor (SHARPIN). RESULTS:A de novo nonsense mutation in IKBKG (c.924C > G; p.Tyr308*) was observed. The Tyr308* mutation inhibited activation of the NF-κB pathway by reducing K63-linked polyubiquitination and linear polyubiquitination. The mutant NEMO was not able to interact with TRAF6, HOIL-1, or SHARPIN. CONCLUSIONS:We identified a novel nonsense IKBKG mutation (c.924C > G; p.Tyr308*) in an IP patient with syndromic tooth agenesis. This research enriches the mutation spectrum of the IKBKG gene.

journal_name

Arch Oral Biol

journal_title

Archives of oral biology

authors

Sun S,Li F,Liu Y,Qu H,Wong SW,Zeng L,Yu M,Feng H,Liu H,Han D

doi

10.1016/j.archoralbio.2019.03.013

subject

Has Abstract

pub_date

2019-05-01 00:00:00

pages

100-107

eissn

0003-9969

issn

1879-1506

pii

S0003-9969(18)30896-3

journal_volume

101

pub_type

杂志文章

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