Background and aim: Mutations in the NKX2.5 gene, a cardiac transcription factor, have been implicated in various types of congenital heart defects (CHD) and it is known that optimal expression levels of this gene are crucial for proper cardiogenesis. However, most of the mutations have been identified in cases of syndromic CHD, and the functional significance of other mutations in this gene has not been studied. We describe in this study the mutational and expression analysis of the NKX2.5 gene in nonsyndromic CHD patients.
Methods: In this study, exon 1 of the NKX2.5 gene was sequenced from 50 probands with sporadic CHD and 50 healthy volunteers. NKX2.5 gene expression levels in blood and cardiac tissue samples were analyzed by reverse transcriptase polymerase chain reaction (RT-PCR) in the probands.
Results: No new mutations were identified; however, a previously reported variant A63G (rs2277923) was found to be present at significantly higher levels in the CHD population than in the control group. Changes in expression between the blood and tissue samples were seen in 37 out of the 50 CHD patients.
Conclusion: Multiple factors, in addition to NKX2.5 gene mutations, may cause CHDs. NKX2.5 gene mutations may be mosaic in nature, therefore warranting investigation in both blood and tissue samples.