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Mutation spectrum of GATA4 associated with congenital atrial septal defects

INTRODUCTION: Congenital atrial septal defect (ASD) is the second commonest form of cardiac developmental anomaly, responsible for substantial morbidity and mortality in affected individuals. Previous studies have implicated genetic defects in the pathogenesis of ASD. However, ASD is largely a genet...

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Autores principales: Yang, Yi-Qing, Wang, Juan, Liu, Xing-Yuan, Chen, Xiao-Zhong, Zhang, Wei, Wang, Xiao-Zhou
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Termedia Publishing House 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3902718/
https://www.ncbi.nlm.nih.gov/pubmed/24482639
http://dx.doi.org/10.5114/aoms.2013.39788
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author Yang, Yi-Qing
Wang, Juan
Liu, Xing-Yuan
Chen, Xiao-Zhong
Zhang, Wei
Wang, Xiao-Zhou
author_facet Yang, Yi-Qing
Wang, Juan
Liu, Xing-Yuan
Chen, Xiao-Zhong
Zhang, Wei
Wang, Xiao-Zhou
author_sort Yang, Yi-Qing
collection PubMed
description INTRODUCTION: Congenital atrial septal defect (ASD) is the second commonest form of cardiac developmental anomaly, responsible for substantial morbidity and mortality in affected individuals. Previous studies have implicated genetic defects in the pathogenesis of ASD. However, ASD is largely a genetically heterogeneous disease and the genetic determinants for ASD in the majority of patients remain to be identified. MATERIAL AND METHODS: The entire coding region of GATA4, a gene encoding a zinc-finger transcription factor essential for normal cardiac morphogenesis, was sequenced in 220 unrelated patients with ASD. The available relatives of the patients harboring the identified mutations and 200 unrelated ethnicity-matched control individuals were genotyped. RESULTS: Four heterozygous missense GATA4 mutations, p.P36S, p.H190R, p.S262A, and p.V399G, were identified in four unrelated patients with ASD, respectively. These mutations were neither detected in 200 control individuals nor described in the human SNP database. Alignment of multiple GATA4 protein sequences across species indicated that the affected amino acids were highly conserved evolutionarily. Genetic analysis of the available relatives of the mutation carriers showed that in each family the mutation co-segregated with ASD. CONCLUSIONS: The findings expand the spectrum of mutations in GATA4 linked to ASD and provide new insight into the molecular etiology associated with ASD, suggesting the potential implications for the genetic diagnosis and gene-specific therapy for this prevalent cardiovascular abnormality in humans.
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spelling pubmed-39027182014-01-30 Mutation spectrum of GATA4 associated with congenital atrial septal defects Yang, Yi-Qing Wang, Juan Liu, Xing-Yuan Chen, Xiao-Zhong Zhang, Wei Wang, Xiao-Zhou Arch Med Sci Basic Research INTRODUCTION: Congenital atrial septal defect (ASD) is the second commonest form of cardiac developmental anomaly, responsible for substantial morbidity and mortality in affected individuals. Previous studies have implicated genetic defects in the pathogenesis of ASD. However, ASD is largely a genetically heterogeneous disease and the genetic determinants for ASD in the majority of patients remain to be identified. MATERIAL AND METHODS: The entire coding region of GATA4, a gene encoding a zinc-finger transcription factor essential for normal cardiac morphogenesis, was sequenced in 220 unrelated patients with ASD. The available relatives of the patients harboring the identified mutations and 200 unrelated ethnicity-matched control individuals were genotyped. RESULTS: Four heterozygous missense GATA4 mutations, p.P36S, p.H190R, p.S262A, and p.V399G, were identified in four unrelated patients with ASD, respectively. These mutations were neither detected in 200 control individuals nor described in the human SNP database. Alignment of multiple GATA4 protein sequences across species indicated that the affected amino acids were highly conserved evolutionarily. Genetic analysis of the available relatives of the mutation carriers showed that in each family the mutation co-segregated with ASD. CONCLUSIONS: The findings expand the spectrum of mutations in GATA4 linked to ASD and provide new insight into the molecular etiology associated with ASD, suggesting the potential implications for the genetic diagnosis and gene-specific therapy for this prevalent cardiovascular abnormality in humans. Termedia Publishing House 2013-12-26 2013-12-30 /pmc/articles/PMC3902718/ /pubmed/24482639 http://dx.doi.org/10.5114/aoms.2013.39788 Text en Copyright © 2013 Termedia & Banach http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-Noncommercial 3.0 Unported License, permitting all non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Basic Research
Yang, Yi-Qing
Wang, Juan
Liu, Xing-Yuan
Chen, Xiao-Zhong
Zhang, Wei
Wang, Xiao-Zhou
Mutation spectrum of GATA4 associated with congenital atrial septal defects
title Mutation spectrum of GATA4 associated with congenital atrial septal defects
title_full Mutation spectrum of GATA4 associated with congenital atrial septal defects
title_fullStr Mutation spectrum of GATA4 associated with congenital atrial septal defects
title_full_unstemmed Mutation spectrum of GATA4 associated with congenital atrial septal defects
title_short Mutation spectrum of GATA4 associated with congenital atrial septal defects
title_sort mutation spectrum of gata4 associated with congenital atrial septal defects
topic Basic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3902718/
https://www.ncbi.nlm.nih.gov/pubmed/24482639
http://dx.doi.org/10.5114/aoms.2013.39788
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