A Novel Gene DUSP8 Missense Mutation Causes Nonsyndromic Hereditary Gingival Fibromatosis by Dysregulating Lysine Lactylation
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Updated: May 30, 2025

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
Xiu Liu1,2, Chao Liang1,3, Shengnan Wang1
1Beijing Institute of Dental Research, Beijing Stomatological Hospital, Capital Medical University, Beijing, China.
Aims:
The goal of this study was to explore new candidate genes and pathogenesis mechanisms of nonsyndromic hereditary gingival fibromatosis (nsHGF) and to provide an experimental basis for the diagnosis of nsHGF.
Methods:
Whole-exome sequencing (WES) was performed on peripheral blood DNA from three nsHGF family members to screen for new candidate genes, and Sanger sequencing and related databases were used to verify the pathogenicity of this gene deficiency. Moreover, the effects of gene deficiency on the biological characteristics of human gingival fibroblasts (HGFs) were evaluated via cell proliferation assays, extracellular matrix (ECM) deposition detection, cell apoptosis and cell cycle assessment, cell migration and gene expression analyses.
Results:
A novel missense mutation in dual-specificity phosphatase 8 (DUSP8, c.1348C>T, p.R450C), which is in the nsHGF-related GINGF4 locus, was identified via WES analysis. A functional study revealed that knocking down DUSP8 expression increased cell proliferation, cell migration and the expression of profibrotic factors (particularly COL1A1), inhibited cell apoptosis, and ultimately resulted in nsHGF. Similarly, this DUSP8 mutation inhibited the expression of the encoded protein and promoted cell proliferation and the expression of profibrotic factors. In addition, both DUSP8 knockdown and DUSP8 mutation induced nsHGF by accelerating glycolysis and panlysine lactylation (Kla) to promote cell proliferation and the expression of ECM-related factors.
Conclusion:
DUSP8 deficiency might be a novel pathogenic factor that contributes to nsHGF.
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