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

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

  • Arch Oral Biol. 2019 May;101:100-107. doi: 10.1016/j.archoralbio.2019.03.013.
Shichen Sun 1,  Fang Li 1,  Yang Liu 1,  Hong Qu 2,  Sing-Wai Wong 3,  Li Zeng 1,  Miao Yu 1,  Hailan Feng 1,  Haochen Liu 4,  Dong Han 5
Affiliations

Affiliations

  • 1 Department of Prosthodontics, Peking University School and Hospital of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, PR China.
  • 2 Center for Bioinformatics, State Key Laboratory of Protein and Plant Gene Research, College of Life Sciences, Peking University, Beijing 100871, PR China.
  • 3 Oral and Craniofacial Biomedicine Curriculum, School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • 4 Department of Prosthodontics, Peking University School and Hospital of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, PR China. Electronic address: talentlhc@163.com.
  • 5 Department of Prosthodontics, Peking University School and Hospital of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, PR China. Electronic address: donghan@bjmu.edu.cn.
PMID: 30913450 DOI: 10.1016/j.archoralbio.2019.03.013
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.

Keywords

IKBKG; Incontinentia pigmenti; Mutation; Syndromic tooth agenesis.

Figures
Products