Novel Point Mutations in 3'-Untranslated Region of GATA4 Gene Are Associated with Sporadic Non-syndromic Atrial and Ventricular Septal Defects.
Curr Med Sci
; 42(1): 129-143, 2022 Feb.
Article
em En
| MEDLINE
| ID: mdl-34652630
ABSTRACT
OBJECTIVE:
Transcription factor GATA4 has significant roles in embryonic heart development. Mutations of GATA4 appear to be responsible for a wide variety of congenital heart defects (CHD). Despite the high prevalence of GATA4 mutations in CHD phenotypes, extensive studies have not been performed. The 3'-untranslated region (3'-UTR) of the GATA4 gene comprises regulatory motifs and microRNA binding sites that are critical for the appropriate gene expression, nuclear transportation, and regulation of translation, and stability of mRNA. This study aimed to evaluate the association between mutations in the 3'-UTR of the GATA4 gene and CHD risk among Iranian patients.METHODS:
We analyzed the coding region of exon 6 and the whole 3'-UTR of GATA4 in DNA isolated from 175 blood samples of CHD patients and 115 unrelated healthy individuals. The functional importance of the observed GATA4 mutations was evaluated using a variety of bioinformatics algorithms for assessment of nonsynonymous mutations and those observed in miRNA binding sites of 3'-UTR.RESULTS:
Twenty-one point mutations including one missense mutation (c.511A>G p.Ser377Gly) in exon 6 and 20 nucleotide variations in 3'-UTR of GATA4 gene were identified in 65 of the 175 CHD patients. In our patients, we identified 12 novel sequence alterations and 8 single nucleotide polymorphisms in the 3'-UTR of GATA4. Most of them had statistically significant differences between CHD patients and controls.CONCLUSION:
Our results suggest that 3'-UTR variations of the GATA4 gene probably change microRNA binding sites and present an additional molecular risk factor for the susceptibility of CHD.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fator de Transcrição GATA4
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Cardiopatias Congênitas
Tipo de estudo:
Etiology_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adolescent
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Adult
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Child
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Child, preschool
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Female
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Humans
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Infant
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Male
País/Região como assunto:
Asia
Idioma:
En
Revista:
Curr Med Sci
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Irã