A Novel Variant in CLCN7 Regulates the Coupling of Angiogenesis and Osteogenesis

Peng, Hui; He, Hongbo; Wen, Ting

doi:10.3389/fcell.2020.599826

Cited by 3 publications

(4 citation statements)

References 49 publications

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“…The mRNAs co-expressed with LA16C-312E8.2 included CCDC154, CLCN7, GNPTG, PERCC1, UNKL, and C16orf91. CCDC154 is mainly involved in osteopetrosis and hypoplastic left heart syndrome ( 37 , 38 ), and CLCN7 is mainly involved in osteopetrosis and angiogenesis ( 39 ). Diseases associated with GNPTG include mucolipidosis III gamma and mucolipidosis ( 40 , 41 ), and those associated with PERCC1 include diarrhea 11, malabsorptive, congenital, and hepatocellular carcinoma ( 42 – 44 ).…”

Section: Discussionmentioning

confidence: 99%

“…UNKL is associated with mucolipidosis ( 45 ), while the function and role of C16orf91 have not been reported. Among these co-expressed mRNAs, GNPTG and UNKL were involved in mucolipidosis that is associated with dilated cardiomyopathy in mucolipidosis type 2 ( 46 ), and CLCN7 was related to angiogenesis ( 39 ). These three genes are associated with cardiovascular diseases but have not been reported in HCM, which may be related to the lack of adequate research on HCM.…”

Section: Discussionmentioning

confidence: 99%

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Identification of key genes for hypertrophic cardiomyopathy using integrated network analysis of differential lncRNA and gene expression

Cao

Liu

2022

Front. Cardiovasc. Med.

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ObjectiveHypertrophic cardiomyopathy (HCM) is a complex heterogeneous heart disease. Recent reports found that long non-coding RNAs (lncRNAs) play an important role in the progression of cardiovascular diseases. The present study aimed to identify the novel lncRNAs and messenger RNAs (mRNAs) and determine the key pathways involved in HCM.MethodsThe lncRNA and mRNA sequencing datasets of GSE68316 and GSE130036 were downloaded from the Gene Expression Omnibus (GEO) database. An integrated co-expression network analysis was conducted to identify differentially expressed lncRNAs and differentially expressed mRNAs in patients with HCM. Then, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were explored to identify the biological functions and signaling pathways of the co-expression network. Protein–protein interaction (PPI) and hub gene networks were constructed by using Cytoscape software. Plasma samples of patients with HCM and the GSE89714 dataset were used to validate the bioinformatics results.ResultsA total of 1,426 differentially expressed long non-coding RNAs (lncRNAs) and 1,715 differentially expressed mRNAs were obtained from GSE68316, of which 965 lncRNAs and 896 mRNAs were upregulated and 461 lncRNAs and 819 mRNAs were downregulated. A total of 469 differentially expressed lncRNAs and 2,407 differentially expressed mRNAs were screened from GSE130036, of which 183 lncRNAs and 1,283 mRNAs were upregulated and 286 lncRNAs and 1,124 mRNAs were downregulated. A co-expression network was constructed and contained 30 differentially expressed lncRNAs and 63 differentially expressed mRNAs, which were primarily involved in ‘G-protein beta/gamma-subunit complex binding,' ‘polyubiquitin modification-dependent protein binding,' ‘Apelin signaling pathway,' and ‘Wnt signaling pathway.' The 10 hub genes in the upregulated network [G Protein Subunit Alpha I2 (GNAI2), G Protein Subunit Alpha I1 (GNAI1), G Protein Subunit Alpha I3 (GNAI3), G Protein Subunit Gamma 2 (GNG2), G Protein Subunit Beta 1 (GNB1), G Protein Subunit Gamma 13 (GNG13), G Protein Subunit Gamma Transducin 1 (GNGT1), G Protein Subunit Gamma 12 (GNG12), AKT Serine/Threonine Kinase 1 (AKT1) and GNAS Complex Locus (GNAS)] and the 10 hub genes in the downregulated network [Nucleotide-Binding Oligomerization Domain Containing Protein 2 (NOD2), Receptor-Interacting Serine/Threonine Kinase 2 (RIPK2), Nucleotide-Binding Oligomerization Domain Containing Protein 1 (NOD1), Mitochondrial Antiviral Signaling Protein (MAVS), Autophagy Related 16-Like 1 (ATG16L1), Interferon Induced With Helicase C Domain 1 (IFIH1), Autophagy Related 5 (ATG5), TANK-Binding Kinase 1 (TBK1), Caspase Recruitment Domain Family Member 9 (CARD9), and von Willebrand factor (VWF)] were screened using cytoHubba. The expression of LA16c-312E8.2 and RP5-1160K1.3 in the plasma of patients with HCM was elevated, and the expression of the MIR22 host gene (MIR22HG) was decreased, which was consistent with our analysis, while the expression of LINC00324 and Small Nucleolar RNA Host Gene 12 (SNHG12) was not significantly different between the two groups. Verification analyses performed on GSE89714 showed the upregulated mRNAs of Chloride Voltage-Gated Channel 7 (CLCN7), N-Acetylglucosamine-1-Phosphate Transferase Subunit Gamma (GNPTG), Unk Like Zinc Finger (UNKL), Adenosine Monophosphate Deaminase 2 (AMPD2), GNAI3, WD Repeat Domain 81 (WDR81), and Serpin Family F Member 1 (SERPINF1) and downregulated mRNAs of TATA-Box Binding Protein Associated Factor 12 (TAF12) co-expressed with five crucial lncRNAs. Moreover, GNAI2, GNAI3, GNG12, and vWF were upregulated and GNAS was downregulated in the top 10 hub genes of upregulated and downregulated PPI networks.ConclusionThese findings from integrative biological analysis of lncRNA-mRNA co-expression networks explored the key genes and pathways and provide new insights into the understanding of the mechanism and discovering new therapeutic targets for HCM. Three differentially expressed pivotal lncRNAs (LA16c-312E8.2, RP5-1160K1.3, and MIR22HG) in the co-expression network may serve as biomarkers and intervention targets for the diagnosis and treatment of HCM.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Identification of key genes for hypertrophic cardiomyopathy using integrated network analysis of differential lncRNA and gene expression

Cao

Liu

2022

Front. Cardiovasc. Med.

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“…A summary of previous reported cases of ADO II patients as well as our case is provided in Table 1 . In addition, several series of family studies are included[ 11 - 24 ]. Based on our summary of the literature, we found more female patients (53% of total) than males.…”

Section: Discussionmentioning

confidence: 99%

Autosomal dominant osteopetrosis type II resulting from a de novo mutation in the CLCN7 gene: A case report

Song¹,

Peng²,

Wang³

et al. 2022

WJCC

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BACKGROUND Osteopetrosis is a family of extremely rare diseases caused by failure of osteoclasts and impaired bone resorption. Among them, autosomal dominant osteopetrosis type II (ADO II), related to the chloride channel 7 ( CLCN7 ) gene, is the most frequent form of osteopetrosis. In this study, we report a de novo mutation of CLCN7 in a patient without the family history of ADO II. CASE SUMMARY A 5-year-old Chinese boy with ADO II was found to have a de novo mutation in the CLCN7 gene [c.746C>T (p.P249L)]. Typical clinical manifestations, including thickening of the cortex of spinal bones and long bones, non-traumatic fracture of the femoral neck, and femoral head necrosis, were found in this patient. The patient is the first reported case of ADO II with the missense mutation c.746C>T (p.P249L) of the CLCN7 gene reported in China. We also review the available literature on ADO II-related CLCN7 mutations, including baseline patient clinical features, special clinical significance, and common mutations. CONCLUSION Our report will enrich the understanding of mutations in ADO II patients. The possibility of a de novo mutation should be considered in individuals who have no family history of osteopetrosis.

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“…Our previous investigation indicated that the knockdown of clcn7 disrupts the balance of the TGF-β/BMP signaling pathway, causing the aforementioned craniofacial bone and tooth defects [ 3 ]. Peng et al [ 75 ] showed that a novel CLCN7 mutation contributed to the increased bone mass by increasing CD31 hi EMCN hi vessel formation and bone formation. These results reveal some novel insights into the pathogenesis and treatment of osteopetrosis with CLCN7 mutations.…”

Section: Molecular Pattern Of Osteopetrosismentioning

confidence: 99%

Molecular Mechanisms of Craniofacial and Dental Abnormalities in Osteopetrosis

Duan

2023

IJMS

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Osteopetrosis is a group of genetic bone disorders characterized by increased bone density and defective bone resorption. Osteopetrosis presents a series of clinical manifestations, including craniofacial deformities and dental problems. However, few previous reports have focused on the features of craniofacial and dental problems in osteopetrosis. In this review, we go through the clinical features, types, and related pathogenic genes of osteopetrosis. Then we summarize and describe the characteristics of craniofacial and dental abnormalities in osteopetrosis that have been published in PubMed from 1965 to the present. We found that all 13 types of osteopetrosis have craniomaxillofacial and dental phenotypes. The main pathogenic genes, such as chloride channel 7 gene (CLCN7), T cell immune regulator 1 (TCIRG1), osteopetrosis-associated transmembrane protein 1 (OSTM1), pleckstrin homology domain-containing protein family member 1 (PLEKHM1), and carbonic anhydrase II (CA2), and their molecular mechanisms involved in craniofacial and dental phenotypes, are discussed. We conclude that the telltale craniofacial and dental abnormalities are important for dentists and other clinicians in the diagnosis of osteopetrosis and other genetic bone diseases.

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A Novel Variant in CLCN7 Regulates the Coupling of Angiogenesis and Osteogenesis

Cited by 3 publications

References 49 publications

Identification of key genes for hypertrophic cardiomyopathy using integrated network analysis of differential lncRNA and gene expression

Identification of key genes for hypertrophic cardiomyopathy using integrated network analysis of differential lncRNA and gene expression

Autosomal dominant osteopetrosis type II resulting from a de novo mutation in the CLCN7 gene: A case report

Molecular Mechanisms of Craniofacial and Dental Abnormalities in Osteopetrosis

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