Novel IKBKG Mutations Identified in Chinese Patients with Syndromic Tooth Agenesis

Objectives: Tooth agenesis is one of the most common anomalies of human dentition. Tooth agenesis may be isolated or present as part of a syndrome. The aim of this research was to explore the gene mutation in Chinese patients with syndromic tooth agenesis-incontinentia pigmenti (IP).

Methods: Sequencing and IKBKG-specific PCR were used to detect IKBKG mutations in two patients with IP. We used the NF-κB reporter gene to assess activation of NF-κB, after transfecting an empty vector, wild-type, or mutant NEMO plasmid into IKBKG-deficient HEK293T cells, respectively. Furthermore, we performed immunoprecipitation and immunoblotting to describe the ubiquitination of NEMO. Lastly, we detected the interactions between mutant NEMO and TRAF6, HOIP, HOIL, and SHARPIN.

Results: A de novo nonsense mutation in IKBKG (c.924C>G; p.Tyr308*) and deletion of exon 4–10 was observed. The Try308* 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, and SHARPIN.

Conclusions: We identified a novel heterozygous nonsense mutation (c.924C>G; p.Tyr308*) and deletion of exon 4–10 of IKBKG in two IP patients in a Chinese population. This is the first report indicating that the IKBKG mutation is responsible for syndromic tooth agenesis in the Chinese population. This research enriches the mutation spectrum of the IKBKG gene.