Congenital heart defects (CHDs) are the most predominant cardiac lesion in pediatric patients.there is an evident suggesting that the risk of congenital heart lesions may be related to NKX 2-5 gene mutations this linkage is most propably
Heart formation is a complex process regulated by many transcription factors. Although most of CHD cases are sporadic, there are several genes which were found to be associated with CHD, including NKX2.5, TBX5, GATA4, etc. Recent studies have identified mutations in these genes which could cause heart developmental anomalies and lead to heart disease. Although cardiac septal defects (CSDs) are common, the precise molecular mechanisms for cardiac septal closure in humans remain to be elucidated
Among these cardiac transcription factors, The NKX2-5 gene on chromosome 5q34 consists of two exons which encode a 324 amino acid protein. This home box transcription factor is expressed during early cardiac morphogenesis and serves as a master regulatory protein
Because of its critical role in cardiogenesis, NKX2-5 has been a prime candidate in studies to identify the genetic basis of structural congenital heart defects. Mutations have been identified in patients with a variety of congenital heart malformations including septal defects, conotruncal abnormalities, cardiomyopathy, and hypoplastic left heart syndrome .
The target of this work was investigating the relation between NKX2-5gene mutations and polymorphism and congenital heart lesions in pediatric patients
This prospective study included 30 children as cases having congenital heart diseases in comparison with 30 children free of any congenital heart lesion as controls history was taken in details through questionnaires. Echocardiography
Was made for each children .children were investigated by DNA analysis for NKX2-5 by means of polymerase chain reaction restricted fragment length polymorphis(PCR-RFLP)
The resulting data from the present study showed that Regarding NKX2-5 rs3729754 SNP, taking CC as a reference, CT, CT+TT genotypes, T allele showed significantly higher frequency in cases when compared to control groups, with significantly higher risk to develop CHD with Pvalue 0.019
No significant differences between cases and control groups regarding NKX2-5 rs104893906 genotypes and alleles.
Also our results declared that among cases 62,6% were found to have CTorTT genotype in comparison to 30% of controls and 30% of cases were found to have CC genotype in comparison to 70% of controls.
On analysis of each group of congenital heart defect seperatly ,there was an association between occurrence of ASD and NKX2-5gene mutations (about 53.3% of cases were ASD 33,3% were VSD 10% were PDA
Also ,the resulting data from this study showed that CA showed the highest frequency, while TC showed the lowest in both cases an control groups.
CHD cases were significantly associated with higher frequency of NKX TC and lower frequency of NKX CA haplotypes.
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