In this experimental study, we studied Kurdish population consisted of 50 healthy with rang 10 - 34 years as control group and 100 (62 females and 38 males) non-syndrome patients, 57 patients (26 males and 31 females) with VSD, 39 patients (12 males and 27 females) with ASD and 4 patients (2 males and 2 females) possessing both defects as case groups with rang 2 - 45 years from Kermanshah Imam Ali cardiovascular hospital and Sanandaj Tohid hospital. In this experimental study, we performed high resolution melt (HRM) mutation scanning of Nkx2-5 exons of non-syndrome patients.ģ. Therefore, the role of Nkx2-5 gene in patients with atrial and ventricular wall defects referred to Sanandaj and Kermanshah hospitals in Kurdish population has been investigated. The cause of CHD in the most cases is unknown, but the molecular evolution and gene analysis of the heart have led to identifying some mutations linked to the CHD. The main purpose of this study determines the role of gene mutations in CHD and genotype-phenotype correlation in ASD and VSD them by HRM, that is a highly effective scanning technique. The technique has already been employed to scan for somatic mutations in the KIT, BRAF, EGFR, ERBB2, TP53 and KRAS genes. It is an in-tube method requiring the inclusion of a saturating intercalating dye in the PCR mix and the addition of a high resolution melt step after PCR. High resolution melting (HRM) is a mutation scanning technique that detects the progressive change in fluorescence caused by the release of an intercalating DNA dye from a DNA duplex as it is denatured by peripheral increases in temperature. Mutations in the cardiac transcription factor, Nkx2-5, were recognized in families who primarily showed non-syndromic ASD and atrioventricular conduction abnormalities. The first genetic etiology for ASD was the discovery that mutations in the transcription factor, TBX5, are a reason of septation defects in the Holt-Oram syndrome, which is characterized by cardiac and upper limb malformations. Monogenic etiologies for ASD and VSD have principally been discovered by studying large families with autosomal dominant forms of septal defects using traditional linkage approaches. Ventricular septal defect (VSD) and atrial septal defect (ASD) are the most common types of CHD and account for 50% of all cases of CHD. This gene has 10,209 bp lengths and contains two exons which encode a protein of 324 amino acids. Nkx2-5, which is a member of Nk home box gene family, locates on chromosome 5q34 and has been preserved during evolution. Mutation in this gene causes atrial and ventricular wall defects, Fallot and tricuspid valve abnormalities. Nkx2-5 also activates synthesis of the other transcription factors such as the members of GATA and MEF2 family. The role of several transcription factors like Nkx2-5, which is the most important one in the progress of mesoderm to the heart tissue, in the processes of cardiac morphogenesis was confirmed. Congenital heart diseases also may be caused in result of defect in different parts of heart. Moreover, CHD is correlated with structural and numeral chromosomal abnormalities (12% - 14%), like 21, 13 and 18 trisomy, turner, etc. Chromosomal and monogenetic abnormalities (about 8%), multifactorial ones (9%) and environmental teratogens (2%) are the main genetic factors for CHD. Complexity in heart development reflects the expression of various genes. Recent genetics studies have shown that many of congenital heart diseases are caused by mutations mainly from a combination of one or more gene interactions with and responses to environment. BackgroundĬongenital heart diseases (CHD) are the most common of all birth defects which contribute substantially to infant mortality, affecting nearly 0.9% of all live births. High Resolution Melt Nkx2-5 Atrial Septal Defect Ventricular Septal Defect 1. It is suggested in further related studies to investigate normal and abnormal cardiac tissue samples of these studied patients and coding genes of the other cardiac transcription factors. The environmental and effective factors on the heart development within embryonic evolution as well as the possibility of the existence of the mutation in coding genes of the other cardiac transcription factors such as GATA4 and TBX5 can be the reasons for the lack of the pathogenic mutation in this study.
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