A novel gene ZNF862 causes hereditary gingival fibromatosis
- Medical School of Nanjing University, China
- BGI Genomics, China
- 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
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.
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.
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.
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A novel gene ZNF862 causes hereditary gingival fibromatosis
eLife 11:e66646.
https://doi.org/10.7554/eLife.66646
Further reading
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- Epidemiology and Global Health
- Genetics and Genomics
Background:
Maternal smoking has been linked to adverse health outcomes in newborns but the extent to which it impacts newborn health has not been quantified through an aggregated cord blood DNA methylation (DNAm) score. Here, we examine the feasibility of using cord blood DNAm scores leveraging large external studies as discovery samples to capture the epigenetic signature of maternal smoking and its influence on newborns in White European and South Asian populations.
Methods:
We first examined the association between individual CpGs and cigarette smoking during pregnancy, and smoking exposure in two White European birth cohorts (n=744). Leveraging established CpGs for maternal smoking, we constructed a cord blood epigenetic score of maternal smoking that was validated in one of the European-origin cohorts (n=347). This score was then tested for association with smoking status, secondary smoking exposure during pregnancy, and health outcomes in offspring measured after birth in an independent White European (n=397) and a South Asian birth cohort (n=504).
Results:
Several previously reported genes for maternal smoking were supported, with the strongest and most consistent association signal from the GFI1 gene (6 CpGs with p<5 × 10-5). The epigenetic maternal smoking score was strongly associated with smoking status during pregnancy (OR = 1.09 [1.07, 1.10], p=5.5 × 10-33) and more hours of self-reported smoking exposure per week (1.93 [1.27, 2.58], p=7.8 × 10-9) in White Europeans. However, it was not associated with self-reported exposure (p>0.05) among South Asians, likely due to a lack of smoking in this group. The same score was consistently associated with a smaller birth size (–0.37±0.12 cm, p=0.0023) in the South Asian cohort and a lower birth weight (–0.043±0.013 kg, p=0.0011) in the combined cohorts.
Conclusions:
This cord blood epigenetic score can help identify babies exposed to maternal smoking and assess its long-term impact on growth. Notably, these results indicate a consistent association between the DNAm signature of maternal smoking and a small body size and low birth weight in newborns, in both White European mothers who exhibited some amount of smoking and in South Asian mothers who themselves were not active smokers.
Funding:
This study was funded by the Canadian Institutes of Health Research Metabolomics Team Grant: MWG-146332.
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- Cancer Biology
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It takes more than 20 years for normal colorectal mucosa to develop into metastatic carcinoma. The long time window provides a golden opportunity for early detection to terminate the malignant progression. Here, we aim to enable liquid biopsy of T1a stage colorectal cancer (CRC) and precancerous advanced adenoma (AA) by profiling circulating small extracellular vesicle (sEV)-derived RNAs. We exhibited a full RNA landscape for the circulating sEVs isolated from 60 participants. A total of 58,333 annotated RNAs were detected from plasma sEVs, among which 1,615 and 888 sEV-RNAs were found differentially expressed in plasma from T1a stage CRC and AA compared to normal controls (NC). Then we further categorized these sEV-RNAs into six modules by a weighted gene coexpression network analysis and constructed a 60-gene t-SNE model consisting of the top 10 RNAs of each module that could well distinguish T1a stage CRC/AA from NC samples. Some sEV-RNAs were also identified as indicators of specific endoscopic and morphological features of different colorectal lesions. The top-ranked biomarkers were further verified by RT-qPCR, proving that these candidate sEV-RNAs successfully identified T1a stage CRC/AA from NC in another cohort of 124 participants. Finally, we adopted different algorithms to improve the performance of RT-qPCR-based models and successfully constructed an optimized classifier with 79.3% specificity and 99.0% sensitivity. In conclusion, circulating sEVs of T1a stage CRC and AA patients have distinct RNA profiles, which successfully enable the detection of both T1a stage CRC and AA via liquid biopsy.
