ArticlePediatric cardiology2012
Genetic and functional analysis of the NKX2-5 gene promoter in patients with ventricular septal defects.
Article in Pediatric cardiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 4 of them syntheses that pooled it.
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Who cites it
18 citing papers in PubMed, 4 syntheses or guidelines pooled it, 30 citations in OpenAlex.
- [Association of single nucleotide polymorphisms of transcription factors with congenital heart diseases in the Chinese population: a Meta analysis].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2018Pooled it
- Associations of NKX2-5 Genetic Polymorphisms with the Risk of Congenital Heart Disease: A Meta-analysis.Pediatric cardiology · 2016Pooled it
- Establishment of Relational Model of Congenital Heart Disease Markers and GO Functional Analysis of the Association between Its Serum Markers and Susceptibility Genes.Computational and mathematical methods in medicine · 2016Pooled it
- Associations between two genetic variants in NKX2-5 and risk of congenital heart disease in Chinese population: a meta-analysis.PloS one · 2013Pooled it
- Combined effects of maternal periconceptional environmental exposures and infant cardiac transcription factor polymorphisms on congenital heart disease risk.Annals of medicine · 2026Article
- Continuous negative autoregulation fine-tunes dosage-sensitive transcription factor expression to maintain post-mitotic neuron identity.bioRxiv : the preprint server for biology · 2026Article
- Analysis of the pathogenicity of novel GNE mutations and clinical, pathological, and genetic characteristics of GNE myopathy in Chinese population.Orphanet journal of rare diseases · 2025Article
- The role of NKX2-5 gene polymorphisms in congenital heart disease (CHD): a systematic review and meta-analysis.The Egyptian heart journal : (EHJ) : official bulletin of the Egyptian Society of Cardiology · 2021Article
- Heart Enhancers: Development and Disease Control at a Distance.Frontiers in genetics · 2021Review
- Axenfeld-Rieger syndrome-associated mutants of the transcription factor FOXC1 abnormally regulateThe Journal of biological chemistry · 2020Article
- Nkx2-5 Regulates the Proliferation and Migration of H9c2 Cells.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- Connection of GLI1 variants to congenital heart disease susceptibility: A case-control study.Medicine · 2020Observational
- Article
- Association of Maternal Diabetes Mellitus and Polymorphisms of theJournal of diabetes research · 2020Article
- Co-occurrence of infantile hypertrophic pyloric stenosis and congenital heart defects: a nationwide cohort study.Pediatric research · 2019Article
- Embryonic protective role of folate in arsenic-induced cardiac malformations in rats.International journal of clinical and experimental pathology · 2018Article
- Gerbode Ventricular Septal Defect -A Rare Cardiac Anomaly Associated with Genetic Variants in Indian Population- A Case Series.Journal of clinical and diagnostic research : JCDR · 2017Article
- Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The ventricular septal defect (VSD) is the most common type of congenital heart disease (CHD). The morbidity and mortality of CHD patients are significantly higher due to late cardiac complications, likely caused by genetic defects. Mutations in cardiac transcription factor genes such as GATA-4, TBX5, and NKX2-5 have been implicated in CHD cases. The NKX2-5 gene, a homeobox gene, is expressed in the developing heart and the adult heart. Because NKX2-5 is a dosage-sensitive regulator during embryonic development, the authors hypothesized that the expression levels of the NKX2-5 gene rather than the mutant protein may play important roles in CHD. In this study, the promoter regions and exon regions of the NKX2-5 gene were bidirectionally sequenced in large cohorts of VSD patients and healthy control subjects. The results showed that a novel sequence variant (g.4574c>deletion), found only in one VSD patient, and a single nucleotide polymorphism (rs118026695), the frequency of which was significantly higher in VSD patients, were identified within the promoter region. Functional analysis confirmed that these sequence variants significantly enhanced the transcriptional activities of the NKX2-5 gene promoter, altering the expression of the NKX2-5 gene and the cardiac gene regulatory network. In addition, a synonymous mutation in the second exon of the NKX2-5 gene was identified in one VSD patient, which may affect the translation process. Therefore, the authors' data provide supportive evidence that mutations in the coding region of the NKX2-5 gene and sequence variants within its promoter region may be among the contributors to the CHD etiology.
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