<i>TBX5</i>mutations contribute to early-onset atrial fibrillation in Chinese and Caucasians

Ji, Fang; Yang, Fan; Mahida, Saagar; Zhao, Ling; Chen, Xiaomin; Zhang, Michael L.; Sun, Zhonghua; Yao, Yan; Zhang, Yi Xin; Zheng, Gu Yan; Dong, Jie; Feng, Ming; Zhang, Rui; Sun, Jian; Li, Shuo; Wang, Qun Shan; H, Cao; Benjamin, Emelia J.; Ellinor, Patrick T.; Li, Yi Gang; Tian, Xiao

doi:10.1093/cvr/cvw003

Cited by 42 publications

(26 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, it is highly expressed in pleuroperitoneal folds, suggesting a role for this gene in diaphragm development, perhaps through interaction with GATA4 and GATA6 that are well‐established CDH genes. In support of its pathogenicity, the identified TBX5:p.(Ser372Leu) variant has been proven to cause a gain of function with an increase of Nppa promoter activation and a drastic reduction of TBX5‐NKX2.5 but not TBX5‐GATA4 physical interaction . Another case of syndromic CDH with aortic coarctation and nonspecified limb defects has been reported in association with variant TBX5:p (Asp111Tyr) .…”

Section: Discussionmentioning

confidence: 96%

“…(Ser372Leu) variant has been proven to cause a gain of function with an increase of Nppa promoter activation 17,29 and a drastic reduction of TBX5-NKX2.5 but not TBX5-GATA4 physical interaction. 17 Another case of syndromic CDH with aortic coarctation and nonspecified limb defects has been reported in association with variant TBX5:p (Asp111Tyr).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Genetic profile of isolated congenital diaphragmatic hernia revealed by targeted next‐generation sequencing

et al. 2018

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Genetic profile of isolated congenital diaphragmatic hernia revealed by targeted next‐generation sequencing

et al. 2018

View full text Add to dashboard Cite

show abstract

“…In aggregate, this is a large increase in the number of loci for which we have a plausible gene target in the relevant tissue type when compared to eQTL studies alone. The results for peakHiCcalled genes were particularly encouraging in the combined analysis of cardiac electrophysiology traits where, in addition to known genes implicated in cardiac electrophysiology such as GJA5 (Christophersen et al, 2013;Gollob et al, 2006) and TBX5 (Ma et al, 2016;Nadadur et al, 2016), a global examination of biological processes associated with the genes identified yielded GO terms centered on the signal conduction and contraction of the myocardium.…”

Section: Connecting Cvd Risk Variants To Genes In the Heart 3d Genomementioning

confidence: 87%

Detailed Regulatory Interaction Map of the Human Heart Facilitates Gene Discovery for Cardiovascular Disease

Bianchi

Geeven

Tucker

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

SummaryMost disease-associated variants identified by population based genetic studies are non-coding, which compromises finding causative genes and mechanisms. Presumably they interact through looping with nearby genes to modulate transcription. Hi-C provides the most complete and unbiased method for genome-wide identification of potential regulatory interactions, but finding chromatin loops in Hi-C data remains difficult and tissue specific data are limited. We have generated Hi-C data from primary cardiac tissue and developed a method, peakHiC, for sensitive and quantitative loop calling to uncover the human heart regulatory interactome. We identify complex CTCF-dependent and -independent contact networks, with loops between coding and non-coding gene promoters, shared enhancers and repressive sites. Across the genome, enhancer interaction strength correlates with gene transcriptional output and loop dynamics follows CTCF, cohesin and H3K27Ac occupancy levels. Finally, we demonstrate that intersection of the human heart regulatory interactome with cardiovascular disease variants facilitates prioritizing disease-causative genes.

show abstract

“…Expression of NPPA was up-regulated in Pitx2 heterozygote and null mice [83]. Further, a recent study in a Chinese population suggested that TBX5 mutations increases the expression of ANP and connexin 40[107]. Senile accumulation of the protein aggregates may contribute to the predisposition to AF with aging.…”

Section: Transcriptomic Analyses and The Age Paradox In Afmentioning

confidence: 99%

Genomics of Atrial Fibrillation

Gutiérrez

Chung

2016

Curr Cardiol Rep

View full text Add to dashboard Cite

Atrial fibrillation (AF) is a common clinical arrhythmia that appears to be highly heritable, despite representing a complex interplay of several disease processes that generally do not manifest until later in life. In this manuscript we will review the genetic basis of this complex trait established through studies of familial AF, linkage and candidate gene studies of common AF, genome wide association studies (GWAS) of common AF, and transcriptomic studies of AF. Since AF is associated with a five-fold increase in the risk of stroke, we also review the intersection of common genetic factors associated with both of these conditions. Similarly, we highlight the intersection of common genetic markers associated with some risk factors for AF, such as hypertension and obesity, and AF. Lastly, we describe a paradigm where genetic factors predispose to the risk of AF, but which may require additional stress and trigger factors in older age to allow for the clinical manifestation of AF.

show abstract

TBX5mutations contribute to early-onset atrial fibrillation in Chinese and Caucasians

Abstract: Our results provide both genetic and functional evidence to support the contribution of TBX5 gene in the pathogenesis of AF. The potential mechanism of arrhythmia may be due in part to the disturbed expression of ANP and CX40.

Cited by 42 publications

References 52 publications

Genetic profile of isolated congenital diaphragmatic hernia revealed by targeted next‐generation sequencing

Genetic profile of isolated congenital diaphragmatic hernia revealed by targeted next‐generation sequencing

Detailed Regulatory Interaction Map of the Human Heart Facilitates Gene Discovery for Cardiovascular Disease

Genomics of Atrial Fibrillation

Contact Info

Product

Resources

About