Dataset Information

Haploinsufficiency of vascular endothelial growth factor related signaling genes is associated with tetralogy of Fallot.

ABSTRACT: PURPOSE:To determine disease-associated single-gene variants in conotruncal defects, particularly tetralogy of Fallot (TOF). METHODS:We analyzed for rare loss-of-function and deleterious variants in FLT4 (VEGFR3) and other genes in the vascular endothelial growth factor (VEGF) pathway, as part of a genome sequencing study involving 175 adults with TOF from a single site. RESULTS:We identified nine (5.1%) probands with novel FLT4 variants: seven loss-of-function, including an 8-kb deletion, and two predicted damaging. In ten other probands we found likely disruptive variants in VEGF-related genes: KDR (VEGFR2; two stopgain and two nonsynonymous variants), VEGFA, FGD5, BCAR1, IQGAP1, FOXO1, and PRDM1. Detection of VEGF-related variants (19/175, 10.9%) was associated with an increased prevalence of absent pulmonary valve (26.3% vs. 3.4%, p?

SUBMITTER: Reuter MS

PROVIDER: S-EPMC6752294 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Haploinsufficiency of vascular endothelial growth factor related signaling genes is associated with tetralogy of Fallot.

Reuter Miriam S MS Jobling Rebekah R Chaturvedi Rajiv R RR Manshaei Roozbeh R Costain Gregory G Heung Tracy T Curtis Meredith M Hosseini S Mohsen SM Liston Eriskay E Lowther Chelsea C Oechslin Erwin E Sticht Heinrich H Thiruvahindrapuram Bhooma B Mil Spencer van SV Wald Rachel M RM Walker Susan S Marshall Christian R CR Silversides Candice K CK Scherer Stephen W SW Kim Raymond H RH Bassett Anne S AS

Genetics in medicine : official journal of the American College of Medical Genetics 20180920 4

<h4>Purpose</h4>To determine disease-associated single-gene variants in conotruncal defects, particularly tetralogy of Fallot (TOF).<h4>Methods</h4>We analyzed for rare loss-of-function and deleterious variants in FLT4 (VEGFR3) and other genes in the vascular endothelial growth factor (VEGF) pathway, as part of a genome sequencing study involving 175 adults with TOF from a single site.<h4>Results</h4>We identified nine (5.1%) probands with novel FLT4 variants: seven loss-of-function, including a ...[more]

PMID: 30232381

Similar Datasets

Project description:Ferroptosis is a newly discovered type of cell death mainly triggered by uncontrolled lipid peroxidation, and it could potentially have a significant impact on the development and progression of tetralogy of Fallot (TOF). Our project aims to identify and validate potential genes related to ferroptosis in TOF. We obtained sequencing data of TOF from the GEO database and ferroptosis-related genes from the ferroptosis database. We employed bioinformatics methods to analyze the differentially expressed mRNAs (DEmRNAs) and microRNAs between the normal control group and TOF group and identify DEmRNAs related to ferroptosis. Protein-protein interaction analysis was conducted to screen hub genes. Furthermore, a miRNA-mRNA-TF co-regulatory network was constructed to utilize prediction software. The expression of hub genes was further validated through quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR). After conducting the differential gene analysis, we observed that in TOF, 41 upregulated mRNAs and three downregulated mRNAs associated with ferroptosis genes were found. Further Gene Ontology/Kyoto Encyclopedia of Genes and Genomes analysis revealed that these genes were primarily involved in molecular functions and biological processes related to chemical stress, oxidative stress, cellular response to starvation, response to nutrient levels, cellular response to external stimulus, and cellular response to extracellular stimulus. Furthermore, we constructed a miRNA-mRNA-TF co-regulatory network. qRT-PCR analysis of the right ventricular tissues from human cases showed an upregulation in the mRNA levels of KEAP1 and SQSTM1. Our bioinformatics analysis successfully identified 44 potential genes that are associated with ferroptosis in TOF. This finding significantly contributes to our understanding of the molecular mechanisms underlying the development of TOF. Moreover, these findings have the potential to open new avenues for the development of innovative therapeutic approaches for the treatment of this condition.

Dataset Information

Haploinsufficiency of vascular endothelial growth factor related signaling genes is associated with tetralogy of Fallot.

Publications

Haploinsufficiency of vascular endothelial growth factor related signaling genes is associated with tetralogy of Fallot.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets