Involvement of a novel GATA4 mutation in atrial septal defects
| العنوان: | Involvement of a novel GATA4 mutation in atrial septal defects |
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| المؤلفون: | Wei-Yi Fang, Jinghao Zheng, Yi-Qing Yang, Kai Bai, Zhong-Min Liu, Juan Wang, Xing-Yuan Liu, Xu Liu, Xiao-Zhou Wang |
| المصدر: | International Journal of Molecular Medicine. |
| بيانات النشر: | Spandidos Publications, 2011. |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | Male, Heterozygote, Molecular Sequence Data, Mutant, Mutation, Missense, Gene mutation, Biology, Heart Septal Defects, Atrial, Atrial septal defects, Mice, Dogs, Genetics, Animals, Humans, Missense mutation, Amino Acid Sequence, Gene, GATA4, Genetic heterogeneity, General Medicine, GATA4 Transcription Factor, Pedigree, Rats, Mutation (genetic algorithm), Cattle, Female |
| الوصف: | Atrial septal defect (ASD) is one of the most common types of congenital heart disease and is associated with a significant increase in the morbidity and mortality of affected individuals. Accumulating evidence indicates that genetic defects play important roles in the pathogenesis of congenital ASD. However, ASD is genetically heterogeneous and the genetic determinants for ASD in the majority of the patients remain to be identified. In this study, the entire coding region of GATA4, a gene encoding a zinc-finger transcription factor crucial to embryogenesis, was initially sequenced in 120 unrelated patients with ASD. The available relatives of patients carrying the identified mutation and 200 ethnicity-matched unrelated control individuals were genotyped. The functional characteristics of the GATA4 mutant were compared to its wild-type counterpart using a luciferase reporter assay system. A novel heterozygous missense GATA4 mutation, p.G21V, was identified in 2 unrelated families with ASD, which was not detected in the control population nor reported in the human gene mutation database. Alignment of multiple GATA4 proteins displayed that the affected amino acid residue was highly conserved across species. Functional analysis showed that the p.G21V GATA4 mutation was associated with a decreased transcriptional activity. The findings underscore the pathogenic link between compromised GATA4 function and congenital ASD, providing new insight into the molecular mechanism involved in this common form of congenital cardiovascular anomalies. |
| تدمد: | 1791-244X 1107-3756 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f6603bda0ca7fbcdd0208ccbef2a2cdfTest https://doi.org/10.3892/ijmm.2011.638Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....f6603bda0ca7fbcdd0208ccbef2a2cdf |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1791244X 11073756 |
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