Investigation of NKX2.5 gene mutations in congenital heart defects in an Indian population.
OBJECTIVE
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.


CONCLUSIONS
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.
1 Department of Human Genetics, Sri Ramachandra University , Chennai, India .
Sarada
S
Ketharnathan
1 Department of Human Genetics, Sri Ramachandra University , Chennai, India .
Teena
T
Koshy
2 Institute of Cardio-Vascular Diseases , The Madras Medical Mission, Chennai, India .
Rajan
R
Sethuratnam
1 Department of Human Genetics, Sri Ramachandra University , Chennai, India .
Solomon
S
Paul
1 Department of Human Genetics, Sri Ramachandra University , Chennai, India .
Vettriselvi
V
Venkatesan
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D006330:Heart Defects, Congenital / Q000097:blood / Q000235:genetics*; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000097:blood / Q000235:genetics*; D006801:Humans; D007194:India; D007223:Infant; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D014157:Transcription Factors / Q000097:blood / Q000235:genetics*
D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; C095552:NKX2-5 protein, human; D014157:Transcription Factors