NKX2-5 variants screening in patients with atrial septal defect in Indonesia

• Main Authors: Anggrahini, D.W (Author), Dinarti, L.K (Author), Gunadi (Author), Hartopo, A.B (Author), Mumpuni, H. (Author), Rozqie, R. (Author), Sadewa, A.H (Author), Satwiko, M.G (Author)
• Format: Article
• Language: English
• Published: BioMed Central Ltd 2022
• Subjects: Arrhythmia; Arrhythmias, Cardiac; Familial ASD; genetics; heart arrhythmia; Heart Septal Defects, Atrial; heart septum defect; Heterozygous variant; homeobox protein Nkx-2.5; Homeobox Protein Nkx-2.5; homeodomain protein; Homeodomain Proteins; human; Humans; Hypertension, Pulmonary; Indonesia; NKX2-5; NKX2-5 protein, human; pulmonary hypertension; Pulmonary hypertension; Variant
• Online Access: View Fulltext in Publisher

 Background: NKX2-5 variant in atrial septal defect patients has been reported. However, it is not yet been described in the Southeast Asian population. Here, we screened the NKX2-5 variants in patients with atrial septal defect (ASD) in the Indonesian population. Method: We recruited 97 patients with ASD for genetic screening of the NKX2-5 variant using Sanger sequencing. Results: We identified three variants of NKX2-5: NM_004387.4:c.63A>G at exon 1, NM_004387.4:c.413G>A, and NM_004387.4:c.561G>C at exon 2. The first variant is commonly found (85.6%) and benign. The last two variants are heterozygous at the same locus. These variants are rare (3.1%) and novel. Interestingly, these variants were discovered in familial atrial septal defects with a spectrum of arrhythmia and severe pulmonary hypertension. Conclusion: Our study is the first report of the NKX2-5 variant in ASD patients in the Southeast Asian population, including a novel heterozygous variant: NM_004387.4:c.413G>A and NM_004387.4:c.561G>C. These variants might contribute to familial ASD risk with arrhythmia and severe pulmonary hypertension. Functional studies are necessary to prove our findings. © 2022, The Author(s).