In silico analysis of GATA4 variants demonstrates main contribution to congenital heart disease.

Introduction: Congenital heart disease (CHD) is the most common congenital abnormality and the main cause of infant mortality worldwide. Some of the mutations that occur in the GATA4 gene region may result in different types of CHD. Here, we report our in silico analysis of gene variants to determin...

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Publicado en:Journal of Cardiovascular & Thoracic Research Vol. 13; no. 4; pp. 336 - 355
Autores principales: Abbasi, Shiva, Mohsen-Pour, Neda, Naderi, Niloofar, Rahimi, Shahin, Maleki, Majid, Kalayinia, Samira
Formato: pictorial research tables/charts Journal Article
Publicado: Tabriz University of Medical Sciences 2021
Acceso en línea:Ver este registro en EBSCOhost
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      dt: 2021
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      pub: Tabriz University of Medical Sciences
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        10.34172/jcvtr.2021.45
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        atl: In silico analysis of GATA4 variants demonstrates main contribution to congenital heart disease.
      aug:
        au:
          Abbasi, Shiva
          Mohsen-Pour, Neda
          Naderi, Niloofar
          Rahimi, Shahin
          Maleki, Majid
          Kalayinia, Samira
        affil: Cardiogenetic Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
      sug:
        subj:
          Transcription Factors
          Heart Defects, Congenital Risk Factors
          Heart Defects, Congenital Familial and Genetic
          Human
          Genomics
          Phylogenetics
          Bioinformatics
          Molecular Structure
      ab: Introduction: Congenital heart disease (CHD) is the most common congenital abnormality and the main cause of infant mortality worldwide. Some of the mutations that occur in the GATA4 gene region may result in different types of CHD. Here, we report our in silico analysis of gene variants to determine the effects of the GATA4 gene on the development of CHD. Methods: Online 1000 Genomes Project, ExAC, gnomAD, GO-ESP, TOPMed, Iranome, GME, ClinVar, and HGMD databases were drawn upon to collect information on all the reported GATA4 variations. The functional importance of the genetic variants was assessed by using SIFT, MutationTaster, CADD, PolyPhen-2, PROVEAN, and GERP prediction tools. Thereafter, network analysis of the GATA4 protein via STRING, normal/mutant protein structure prediction via HOPE and I-TASSER, and phylogenetic assessment of the GATA4 sequence alignment via ClustalW were performed. Results: The most frequent variant was c.874T > C (45.58%), which was reported in Germany. Ventricular septal defect was the most frequent type of CHD. Out of all the reported variants of GATA4, 38 variants were pathogenic. A high level of pathogenicity was shown for p.Gly221Arg (CADD score = 31), which was further analyzed. Conclusion: The GATA4 gene plays a significant role in CHD; we, therefore, suggest that it be accorded priority in CHD genetic screening.
      pubtype: Academic Journal
      doctype:
        pictorial
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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