RGD Reference Report - Molecular mechanisms of Ellis‑van Creveld gene variations in ventricular septal defect. - Rat Genome Database

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Molecular mechanisms of Ellis‑van Creveld gene variations in ventricular septal defect.

Authors: Liu, Fadi  Liu, Xiao  Xu, Zhenyan  Yuan, Ping  Zhou, Qiongqiong  Jin, Jiejing  Yan, Xia  Xu, Zixuan  Cao, Qing  Yu, Jianhua  Cheng, Yingzhang  Wan, Rong  Hong, Kui 
Citation: Liu F, etal., Mol Med Rep. 2018 Jan;17(1):1527-1536. doi: 10.3892/mmr.2017.8088. Epub 2017 Nov 15.
RGD ID: 155260289
Pubmed: PMID:29257216   (View Abstract at PubMed)
PMCID: PMC5780092   (View Article at PubMed Central)
DOI: DOI:10.3892/mmr.2017.8088   (Journal Full-text)

The Ellis-van Creveld (EVC) gene is associated with various congenital heart diseases. However, studies on EVC gene variations in ventricular septal defect (VSD) and the underlying molecular mechanisms are sparse. The present study detected 11 single‑nucleotide polymorphisms (SNPs) in 65 patients with VSD and 210 control patients from the Chinese Han population. Of the identified SNPs only the c.1727G>A SNP site was positively associated with the development of VSD (P<0.007). A known mutation, c.343C>G, was also identified, which causes a leucine to valine substitution at amino acid 115 of the EVC protein (p.L115V). The results of functional prediction indicated that c.343C>G may be a pathogenic mutation. In addition, in NIH3T3 mouse embryonic fibroblast cells, the EVC c.343C>G mutation significantly decreased cell proliferation and increased apoptosis. Further investigation demonstrated that in NIH3T3 cells, overexpression of EVC c.343C>G mutation reduced the binding between EVC and smoothened, which further downregulated the activity of the hedgehog (Hh) signaling pathway and the expression of downstream cyclin D1 and B‑cell lymphoma 2 proteins with SAG. The c.1727G>A SNP of the EVC gene increased VSD susceptibility in patients from the Chinese Han population. The molecular mechanism underlying the development of VSD induced by the EVC c.343C>G mutation may be due to a reduction in the anti‑apoptotic and proliferative abilities of cardiomyocytes via downregulation of Hh pathway activity. The results of the present study may provide novel targets for the diagnosis and treatment of patients with VSD.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
EVCHumanventricular septal defect  IAGP DNA:SNP::c.1727G>A(human)RGD 
EvcRatventricular septal defect  ISOEVC (Homo sapiens)DNA:SNP::c.1727G>A(human)RGD 
EvcMouseventricular septal defect  ISOEVC (Homo sapiens)DNA:SNP::c.1727G>A(human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Evc  (EvC ciliary complex subunit 1)

Genes (Mus musculus)
Evc  (EvC ciliary complex subunit 1)

Genes (Homo sapiens)
EVC  (EvC ciliary complex subunit 1)


Additional Information