NKX2-5 molecular screening and assessment of variant rate and risk  factors of secundum atrial septal defect in a Moroccan population

Bouchikhi, Ihssane El; Bouguenouch, Laila; Moufid, Fatima Zohra; Houssaini, Mohammed Iraqui; Belhassan, Khadija; Samri, Imane; Joutei, Ayoub Tahri; Ouldim, Karim; Atmani, S.

doi:10.14744/anatoljcardiol.2016.7222

Cited by 3 publications

(4 citation statements)

References 47 publications

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“…In this study, it was frequently found that as much as 85.6% of research subjects. This result is the most significant number after research in the population in China, 80.18%, but it was found lower in Germany (59.4%) and Morocco (56.2%) [7,8,11,12].…”

Section: Discussionmentioning

confidence: 77%

“…Previous studies have reported a genetic variant of NKX2-5 linked to the development of atrial septal defect [6,7]. The frequency of gene variant of NKX2-5 in ASD patients with familial history could reach up to 8% and only 1-4% in sporadic cases [8]. Familial genetic variants can be detected earlier, so the management is possible to be carried out before complications appear.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

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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.

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Section: Discussionmentioning

confidence: 77%

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

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“…Three synonymous variations in NKX2-5 are significantly associated with cases compared to controls in our cohort. Earlier reports also suggest the implication of synonymous variants of NKX2-5 in disease pathogenesis (Belvís et al, 2009;Boldt et al, 2010;Posch et al, 2008;El Bouchikhi et al, 2017). However, studies confirming their potential downstream effects are not well documented.…”

Section: Discussionmentioning

confidence: 99%

Functional analysis of novel genetic variants of NKX2‐5 associated with nonsyndromic congenital heart disease

Dixit

Narasimhan

Balekundri³

et al. 2021

American J of Med Genetics Pt A

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NKX2-5, a master cardiac regulatory transcription factor was the first known genetic cause of congenital heart diseases (CHDs). To further investigate its role in CHD pathogenesis, we performed mutational screening of 285 CHD probands and 200 healthy controls. Five coding sequence variants were identified in six CHD cases (2.1%), including three in the N-terminal region (p.A61G, p.R95L, and p.E131K) and one each in homeodomain (HD) (p.A148E) and tyrosine-rich domain (p.P247A). Variant-p.A148E showed tertiary structure changes and differential DNA binding affinity of mutant compared to wild type. Two N-terminal variants-p.A61G and p.E131K along with HD variant p.A148E demonstrated significantly reduced transcriptional activity of Nppa and Actc1 promoters in dual luciferase promoter assay supported by their reduced expression in qRT-PCR. Nonetheless, variant p.R95L affected the synergy of NKX2-5 with serum response factor and TBX5 leading to significantly decreased Actc1 promoter activity depicting a distinctive role of this region.The aberrant expression of other target genes-Irx4, Mef2c, Bmp10, Myh6, Myh7, and Myocd is also observed in response to NKX2-5 variants, possibly due to the defective gene regulatory network. Severely impaired downstream promoter activities and abnormal expression of target genes due to N-terminal variants supports the emerging role of this region during cardiac-developmental pathways.

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“…There are many inconsistencies in the published study results regarding the role of rs2277923 in the NKX2-5 gene, including Iranian [ 14 ] Asian [ 15 ] Moroccan [ 16 ], and Caucasian population [ 17 ]; hence, it is needed to analyze all the available published literature that provide us the most definite results for the role of rs2277923 polymorphism in congenital heart diseases.…”

Section: Introductionmentioning

confidence: 99%

The role of NKX2-5 gene polymorphisms in congenital heart disease (CHD): a systematic review and meta-analysis

Ashiq

Sabar

2021

Egypt Heart J

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Background The gene NKX2-5 is a key transcription factor that plays an essential role in normal cardiac development. Although some recent studies have studied the role of polymorphisms in the NKX2-5 gene in congenital heart diseases (CHDs), the results were not consistent and remained uncertain. Therefore, we conduct a review of literature and investigate the association of genetic polymorphisms with CHDs. Results We selected seventeen studies regarding the association of NKX2-5 gene rs2277923 polymorphism with CHDs. Overall, in all the tested genetic models, the 63A > G polymorphism was not significantly associated with increased congenital heart defects risk. We used pooled odds ratios (OR) to calculate the association of CHDs with rs2277923 including allelic model: OR 1.00, 95% CI 0.82–1.21; homozygote model: OR 0.95, 95%CI 0.68–1.33, recessive model: OR 0.89 CI 0.70–1.13, heterozygote model: OR: 1.09, 95%CI 0.87–1.37, dominant model: OR 1.08 CI 0.82–1.42 and overdominant model: OR 1.17 CI 1.01–1.35. In addition, our analysis suggests that no publication bias exists in this meta-analysis. Conclusions Our findings suggested that 63A > G polymorphism in the NKX2-5 gene was not significantly associated with congenital heart defects. However, in the future, more studies with increased sample size are required that may provide us more definite conclusions.

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NKX2-5 molecular screening and assessment of variant rate and risk factors of secundum atrial septal defect in a Moroccan population

Cited by 3 publications

References 47 publications

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

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

Functional analysis of novel genetic variants of NKX2‐5 associated with nonsyndromic congenital heart disease

The role of NKX2-5 gene polymorphisms in congenital heart disease (CHD): a systematic review and meta-analysis

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