Novel mutations of AXIN2 identified in a Chinese Congenital Heart Disease Cohort

Zhu, Meiying; Ma, Xiaoyun; Ding, Peicheng; Tang, Hanfei; Peng, Rui; Lü, Lei; Li, Peiqiang; Qiao, Bin; Yang, Xueyan; Zheng, Yufang; Wang, Hongyan; Gao, Yun‐Qian; Chen, Feng-Shan

doi:10.1038/s10038-019-0572-x

Cited by 15 publications

(18 citation statements)

References 28 publications

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“…The well-established environmental factors underlying CHD include maternal conditions (such as innutrition, viral infection and endocrine disorder) and exposures to toxic chemicals, therapeutic drugs, or ionizing radiation during pregnancy (Patel and Burns, 2013). However, increasing studies underscore the genetic defects underpinning CHD, and variations in over 70 genes, encompassing those encoding transcription factors, signaling molecules, and sarcomeric proteins, have been involved in CHD (Bashamboo et al, 2018;Cantù et al, 2018;Jaouadi et al, 2018;Li et al, 2018a,c;Lombardo et al, 2018;Manheimer et al, 2018;Pierpont et al, 2018;Razmara and Garshasbi, 2018;Stephen et al, 2018;Xu et al, 2018;Yu Z et al, 2018;Alankarage et al, 2019;Gao et al, 2019;Kalayinia et al, 2019Kalayinia et al, , 2020Ma et al, 2019;Wang J et al, 2019, Wang Z et al, 2019Watkins et al, 2019;Zhu et al, 2019;Faucherre et al, 2020;Shabana et al, 2020;Zhao et al, 2020). Among the recognized CHD-causative genes, the majority code for cardiac transcription factors, encompassing TBX5, GATA4, and NKX2-5 (Li and Yang, 2017).…”

Section: Introductionmentioning

confidence: 99%

A novel TBX5 mutation predisposes to familial cardiac septal defects and atrial fibrillation as well as bicuspid aortic valve

Jiang

Zhao

et al. 2020

Genet. Mol. Biol.

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Section: Introductionmentioning

confidence: 99%

A novel TBX5 mutation predisposes to familial cardiac septal defects and atrial fibrillation as well as bicuspid aortic valve

Jiang

Zhao

et al. 2020

Genet. Mol. Biol.

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“…Also, the mentioned variant was previously associated with cancer risk, such as colorectal cancer [ 30 ], breast cancer [ 31 ], and Hirschsprung disease [ 32 ]. In the case of CHDs patients, other AXIN 2 variants [c.28 C > T (p.L10F), c.395 A > G (p.K132R)] were previously reported by Zhu M et al [ 33 ] as pathogenic variants for CHDs.…”

Section: Discussionmentioning

confidence: 95%

Significant Associations between AXIN1 rs1805105, rs12921862, rs370681 Haplotypes and Variant Genotypes of AXIN2 rs2240308 with Risk of Congenital Heart Defects

Crauciuc

Iancu

Olah

et al. 2020

IJERPH

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This study aimed to investigate possible associations of the susceptibility to congenital heart defects (CHDs) with AXIN1 rs1805105, rs12921862 and rs370681 gene variants and haplotypes, and AXIN2 rs2240308 gene variant. Significant associations were identified for AXIN1 rs370681 and AXIN2 rs2240308 variants. AXIN1 rs370681 variant was significantly associated with decreased odds of CHDs (adjusted OR varying from 0.13 to 0.28 in codominant, dominant and recessive gene models), while the AXIN2 rs2240308 variant was associated with increased odds of CHD in the dominant model. The haplotype-based generalized linear model regression of AXIN1 rs1805105, rs12921862 and rs370681 variants revealed that C-C-C and C-C-T haplotypes significantly increased the risk of CHDs (p < 0.05). No significant second order epistatic interactions were found between investigated variants (AXIN1 rs1805105, rs12921862, rs370681, and AXIN2 rs2240308). Our conclusion is that AXIN1 rs1805105, rs12921862, and rs370681 (C-C-C and C-C-T) haplotypes and AXIN2 rs2240308 contribute to CHDs susceptibility.

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“…Dieldrin (legacy organochlorine pesticide that is persistent in the environment) constitutively activates Akt/mTOR signalling, induces genes associated with cardiovascular dysfunction and compromised lysosomal physiology, thereby identifying a novel mechanism for pesticide-induced cardiotoxicity in the adult zebrafish heart (Slade et al 2017). Rare mutations in AXIN2 (direct target of Wnt/b-catenin pathway) might contribute to the risk of human congenital heart defects, and a balanced canonical Wnt pathway is critical for cardiac development process (Zhu et al 2019). Continuous overexpression of the zebrafish homologous mutation bmpr1aa (p.R438H) within endocardium causes a reduced atrioventricular valve (AV) area, a downregulation of Wnt/b-catenin signalling at the AV canal and growth of additional tissue mass in adult zebrafish hearts (Demal et al 2019).…”

Section: Signalling Pathways Involved In Cardiac Dysfunctionmentioning

confidence: 99%

“…Rare mutations in AXIN2 (direct target of Wnt/β‐catenin pathway) might contribute to the risk of human congenital heart defects, and a balanced canonical Wnt pathway is critical for cardiac development process (Zhu et al . 2019). Continuous overexpression of the zebrafish homologous mutation bmpr1aa (p.R438H) within endocardium causes a reduced atrioventricular valve (AV) area, a downregulation of Wnt/β‐catenin signalling at the AV canal and growth of additional tissue mass in adult zebrafish hearts (Demal et al .…”

Section: Signalling Pathways Involved In Cardiac Dysfunctionmentioning

confidence: 99%

Decades‐long involvement of signalling pathways in cardiovascular research using zebrafish model and its global trends

Binesh

2020

Reviews in Aquaculture

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Research on zebrafish as a model system began a few decades ago, and later, studies on zebrafish developmental biology and genetics resulted in the characterization of a large number of genes involved in vertebrate development and cell signalling pathways, thus establishing zebrafish as a relevant human disease model for research. Cardiovascular diseases (CVDs) are the first leading cause of death and are expected to rise over 23.6 million by 2030. Environmental toxicants such as drugs, alcohols and chemicals can activate/disrupt number of signalling pathways, led to the cardiovascular toxicity and perturb the development of myocardium, cardiomyocytes, cardiac valve formation and cardiac trabecular growth. Based on the total publication output, USA's contribution to cardiovascular research using zebrafish as a model organism was immense compared to that of other countries. Harvard University contributed comprehensive research on CVD using zebrafish model with a cumulative occurrence of keywords like zebrafish, angiogenesis, cardiovascular disease, pollutants and developmental process. Many pathways are redundant, and the activation of certain targets implicated in cardiovascular disease development is by inhibiting one particular pathway leading to activation of alternative signalling pathways. Targeting highly specific pathways by single compounds inhibiting only one protein generally leads to resistance to this therapeutic agent. It is understood from the publications and citations, that the use of zebrafish as a cardiovascular disease (CVD) model has been gradually expanded from 2000 to 2019, likely due to the recapitulated pathophysiology of the human heart.

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Novel mutations of AXIN2 identified in a Chinese Congenital Heart Disease Cohort

Cited by 15 publications

References 28 publications

A novel TBX5 mutation predisposes to familial cardiac septal defects and atrial fibrillation as well as bicuspid aortic valve

A novel TBX5 mutation predisposes to familial cardiac septal defects and atrial fibrillation as well as bicuspid aortic valve

Significant Associations between AXIN1 rs1805105, rs12921862, rs370681 Haplotypes and Variant Genotypes of AXIN2 rs2240308 with Risk of Congenital Heart Defects

Decades‐long involvement of signalling pathways in cardiovascular research using zebrafish model and its global trends

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