The Contribution of Gene Mutations to the Pathogenesisof Tetralogy of Fallot

Amin Safari-Arababadi,Mojtaba Jaafarinia,Seyed Mehdi Kalantar,Mostafa Behjati-Ardakani

doi:10.15171/ijbsm.2019.10

Abstract

Congenital heart disease (CHD) is considered as an important and developing area in the medical community. Since these patients can reach maturity and have children, the role of genetic determinants in increasing risk of CHD is extremely evident among children of these patients. Because genetic studies related to CHD are increasing, and each day the role of new genetic markers is more and more clarified, this review re-examined the effects of gene mutations in the pathogenesis of tetralogy of Fallot (TOF) as an important pathological model among other CHDs. Due to the complexity of heart development, it is not astonishing that numerous signaling pathways and transcription factors, and many genes are involved in pathogenesis of TOF. This review focuses on the jag1, nkx2.5, gata4, zfpm2/fog2 and cited2 genes previously reported to be involved in TOF.

Highlights

Tetralogy of Fallot (TOF; OMIM# 187500) is the most frequent type of congenital heart disease (CHD)
Because genetic studies related to Congenital heart disease (CHD) are increasing, and each day the role of new genetic markers is more and more clarified, this review re-examined the effects of gene mutations in the pathogenesis of tetralogy of Fallot (TOF) as an important pathological model among other CHDs
This review focuses on the jag[1], nkx2.5, gata[4], zfpm2/fog[2] and cited[2] genes previously reported to be involved in TOF

Summary

Introduction

Tetralogy of Fallot (TOF; OMIM# 187500) is the most frequent type of congenital heart disease (CHD). TOF is one of the first CHDs repaired by corrective surgery; females and males are involved. TOF is named after French physician Dr Etienne-Louis Arthur Fallot, who defined a panel of 3 cyanotic patients in 1888 with 4 anatomical characteristics: stenosis of the pulmonary artery, overriding aorta, right ventricular hypertrophy, and ventricular septal defect (VSD).[1,2] In addition to genetic characteristics, the cause of TOF is not exactly clear due to the interference of other factors, such as environmental factors. TOF has been observed in the context of several syndromes including Alagille syndrome (AGS), Trisomy 21, CHARGE (coloboma, heart, atresia of the nasal, retarded, genital, ear abnormalities) and DiGeorge syndromes. 20% of TOF cases are related to genetic syndromes.[1,4,5] The presence of mutations in genes Jagged[1] (JAG1), NK2 Homeobox 5 (NKX2.5), binding protein GATA (GATA), zinc finger protein, FOG family member 2 (ZFPM2/FOG2), Cbp/p300-interacting transactivator with Glu/Asprich carboxyterminal domain 2 (CITED2) and variants of other genes and the interaction between genetic and environmental factors underly the pathogenesis of TOF.[6,7,8] this review addresses current information regarding the roles of variations in JAG1, NKX2.5, GATA4, ZFPM2/FOG2 and CITED2 genes in the pathogenesis of TOF

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Conclusion