OR1. A novel double heterozygote variation of NKX2-5 gene in adult patients with atrial septal defect

Abstract

Abstract Background and Aim It is still unclear whether the NKX2-5 variant is involved in congenital heart disease patients in Indonesia. Here, we investigate the genetic variation of NKX2-5 in adult atrial septal defect (ASD) patients at RSUP Dr Sardjito Yogyakarta, Indonesia. Methods and Results We screened 97 patients with ASD for genetic variations of NKX2-5. DNA samples were extracted from venous blood. The whole two coding exons of the NKX2-5 gene were amplified by PCR and sequenced using the Sanger method. The sequence was compared with the reference genome taken from NCBI using SerialCloner software. We identified three NKX2-5 genetic variants: c.63 A>G (rs2277923) at exon 1, c.413 G>A (rs1366528649) and c.561G>A (rs767559311) at exon 2. The variation in rs2277923 was detected in 83 patients (85.6%), including 41 subjects (42.3%) with heterozygous A>G and 42 subjects (43. 3%) with homozygous A>G. However, it has a similar amino acid sequence. The variant of rs1366528649 and rs767559311 were heterozygous and found in the same locus (double heterozygous variation). Interestingly, rs1366528649 and rs767559311 were only identified in familial ASD (3 patients, 3,1%). The rs1366528649 variant replaces arginine (a basic amino acid) with glutamine (an acidic amino acid). Meanwhile, the rs767559311 variant substitutes glutamine with histidine (a basic amino acid). Conclusion We discovered a novel double heterozygote variation of the NKX2-5 gene (rs1366528649 and rs767559311) and may contribute to familial ASD risk. Moreover, rs2277923 is the most common variation in ASD patients in Indonesia.