A novel gene ZNF862 causes hereditary gingival fibromatosis

  1. Juan Wu
  2. Dongna Chen
  3. Hui Huang
  4. Ning Luo
  5. Huishuang Chen
  6. Junjie Zhao
  7. Yanyan Wang
  8. Tian Zhao
  9. Siyuan Huang
  10. Yang Ren
  11. Teng Zhai
  12. Weibin Sun
  13. Houxuan Li  Is a corresponding author
  14. Wei Li  Is a corresponding author
  1. Medical School of Nanjing University, China
  2. BGI Genomics, China
  3. Peking University, China

Abstract

Hereditary gingival fibromatosis (HGF) is the most common genetic form of gingival fibromatosis which is featured as a localized or generalized overgrowth of gingivae. Currently two genes (SOS1 and REST), as well as four loci (2p22.1, 2p23.3-p22.3, 5q13-q22, and 11p15), have been identified as associated with HGF in a dominant inheritance pattern. Here we report thirteen individuals with autosomal-dominant HGF from a four-generation Chinese family. Whole-exome sequencing followed by further genetic co-segregation analysis was performed for the family members across three generations. A novel heterozygous missense mutation (c.2812G>A) in zinc finger protein 862 gene (ZNF862) was identified, and it is absent among the population as per the Genome Aggregation Database. The functional study supports a biological role of ZNF862 for increasing the profibrotic factors particularly COL1A1 synthesis and hence resulting in HGF. Here for the first time we identify the physiological role of ZNF862 for the association with the HGF.

Data availability

The sequencing data supporting this study have been deposited in the China Genebank Nucleotide Sequence Archive (https://db.cngb.org/cnsa, accession number CNP0000995).

Article and author information

Author details

  1. Juan Wu

    Department of Periodontology, Medical School of Nanjing University, Nanjing, China
    Competing interests
    No competing interests declared.
  2. Dongna Chen

    Clinical research, BGI Genomics, Shenzhen, China
    Competing interests
    Dongna Chen, is employee of BGI Genomics..
  3. Hui Huang

    Clinical research, BGI Genomics, Shenzhen, China
    Competing interests
    Hui Huang, is employee of BGI Genomics..
  4. Ning Luo

    Department of Periodontology, Medical School of Nanjing University, Nanjing, China
    Competing interests
    No competing interests declared.
  5. Huishuang Chen

    Clinical research, BGI Genomics, Shenzhen, China
    Competing interests
    Huishuang Chen, is employee of BGI Genomics..
  6. Junjie Zhao

    Department of Periodontology, Medical School of Nanjing University, Nanjing, China
    Competing interests
    No competing interests declared.
  7. Yanyan Wang

    Clinical research, BGI Genomics, Shenzhen, China
    Competing interests
    Yanyan Wang, is employee of BGI Genomics..
  8. Tian Zhao

    Department of Periodontology, Medical School of Nanjing University, shenzhen, China
    Competing interests
    No competing interests declared.
  9. Siyuan Huang

    Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China
    Competing interests
    No competing interests declared.
  10. Yang Ren

    Department of Periodontology, Medical School of Nanjing University, Nanjing, China
    Competing interests
    No competing interests declared.
  11. Teng Zhai

    Clinical research, BGI Genomics, shenzhen, China
    Competing interests
    Teng Zhai, is employee of BGI Genomics..
  12. Weibin Sun

    Department of Periodontology, Medical School of Nanjing University, shenzhen, China
    Competing interests
    No competing interests declared.
  13. Houxuan Li

    Department of Periodontology, Medical School of Nanjing University, Nanjing, China
    For correspondence
    lihouxuan3435_0@163.com
    Competing interests
    No competing interests declared.
  14. Wei Li

    Clinical Research, BGI Genomics, Shen zhen, China
    For correspondence
    liwei10@genomics.cn
    Competing interests
    Wei Li, is employee of BGI Genomics..
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4475-531X

Funding

National Natural Science Foundation of China (51772144)

  • Houxuan Li

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Beate Maria Lichtenberger, Medical University of Vienna, Austria

Ethics

Human subjects: The usage and handling of human samples in this study was approved by the Institutional Review Board on Bioethics and Biosafety of BGI (IRB No. 19059) and the written informed consent obtained from each participant. Clinical investigation was performed in accordance with the Declaration of Helsinki.

Version history

  1. Preprint posted: May 1, 2020 (view preprint)
  2. Received: January 19, 2021
  3. Accepted: February 9, 2022
  4. Accepted Manuscript published: February 10, 2022 (version 1)
  5. Accepted Manuscript updated: February 15, 2022 (version 2)
  6. Version of Record published: February 18, 2022 (version 3)

Copyright

© 2022, Wu et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 699
    Page views
  • 121
    Downloads
  • 5
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Juan Wu
  2. Dongna Chen
  3. Hui Huang
  4. Ning Luo
  5. Huishuang Chen
  6. Junjie Zhao
  7. Yanyan Wang
  8. Tian Zhao
  9. Siyuan Huang
  10. Yang Ren
  11. Teng Zhai
  12. Weibin Sun
  13. Houxuan Li
  14. Wei Li
(2022)
A novel gene ZNF862 causes hereditary gingival fibromatosis
eLife 11:e66646.
https://doi.org/10.7554/eLife.66646

Share this article

https://doi.org/10.7554/eLife.66646

Further reading

    1. Genetics and Genomics
    Songyuan Wu, Xiaoling Tong ... Fangyin Dai
    Research Article

    The color pattern of insects is one of the most diverse adaptive evolutionary phenotypes. However, the molecular regulation of this color pattern is not fully understood. In this study, we found that the transcription factor Bm-mamo is responsible for black dilute (bd) allele mutations in the silkworm. Bm-mamo belongs to the BTB zinc finger family and is orthologous to mamo in Drosophila melanogaster. This gene has a conserved function in gamete production in Drosophila and silkworms and has evolved a pleiotropic function in the regulation of color patterns in caterpillars. Using RNAi and clustered regularly interspaced short palindromic repeats (CRISPR) technology, we showed that Bm-mamo is a repressor of dark melanin patterns in the larval epidermis. Using in vitro binding assays and gene expression profiling in wild-type and mutant larvae, we also showed that Bm-mamo likely regulates the expression of related pigment synthesis and cuticular protein genes in a coordinated manner to mediate its role in color pattern formation. This mechanism is consistent with the dual role of this transcription factor in regulating both the structure and shape of the cuticle and the pigments that are embedded within it. This study provides new insight into the regulation of color patterns as well as into the construction of more complex epidermal features in some insects.

    1. Chromosomes and Gene Expression
    2. Genetics and Genomics
    Maria L Adelus, Jiacheng Ding ... Casey E Romanoski
    Research Article

    Heterogeneity in endothelial cell (EC) sub-phenotypes is becoming increasingly appreciated in atherosclerosis progression. Still, studies quantifying EC heterogeneity across whole transcriptomes and epigenomes in both in vitro and in vivo models are lacking. Multiomic profiling concurrently measuring transcriptomes and accessible chromatin in the same single cells was performed on six distinct primary cultures of human aortic ECs (HAECs) exposed to activating environments characteristic of the atherosclerotic microenvironment in vitro. Meta-analysis of single-cell transcriptomes across 17 human ex vivo arterial specimens was performed and two computational approaches quantitatively evaluated the similarity in molecular profiles between heterogeneous in vitro and ex vivo cell profiles. HAEC cultures were reproducibly populated by four major clusters with distinct pathway enrichment profiles and modest heterogeneous responses: EC1-angiogenic, EC2-proliferative, EC3-activated/mesenchymal-like, and EC4-mesenchymal. Quantitative comparisons between in vitro and ex vivo transcriptomes confirmed EC1 and EC2 as most canonically EC-like, and EC4 as most mesenchymal with minimal effects elicited by siERG and IL1B. Lastly, accessible chromatin regions unique to EC2 and EC4 were most enriched for coronary artery disease (CAD)-associated single-nucleotide polymorphisms from Genome Wide Association Studies (GWAS), suggesting that these cell phenotypes harbor CAD-modulating mechanisms. Primary EC cultures contain markedly heterogeneous cell subtypes defined by their molecular profiles. Surprisingly, the perturbations used here only modestly shifted cells between subpopulations, suggesting relatively stable molecular phenotypes in culture. Identifying consistently heterogeneous EC subpopulations between in vitro and ex vivo models should pave the way for improving in vitro systems while enabling the mechanisms governing heterogeneous cell state decisions.