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. 2017 Mar;17(3):217-223.
doi: 10.14744/AnatolJCardiol.2016.7222. Epub 2016 Oct 12.

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

Ihssane El Bouchikhi  1 , Laila Bouguenouch  2 , Fatima Zohra Moufid  3 , Mohammed Iraqui Houssaini  4 , Khadija Belhassan  2 , Imane Samri  2 , Ayoub Tahri Joutei  4 , Karim Ouldim  2 , Samir Atmani  5
Affiliations

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

Ihssane El Bouchikhi et al. Anatol J Cardiol. 2017 Mar.

Abstract

Objective: Secundum atrial septal defect (ASDII) has multifactorial etiology that is combination of environmental (e.g., mother's exposure to toxicity, ethnicity) and genetic causes. Aim of the present study was to screen a Moroccan population with ASDII for NKX2-5 variants and to assess risk factors that may contribute to emergence of the disorder.

Methods: Thirty-two non-syndromic ASDII patients were screened for NKX2-5 variants using direct sequencing of polymerase chain reactionamplified coding regions. Risk factor rates were compared to general population and assessed using Fisher's exact and chi-square tests. In this retrospective study, criteria of exclusion were suggestive or confirmed syndrome association.

Results: Three heterozygous variants were detected in 4 patients. NKX2-5 variant rate in present cohort is estimated to be about 9.4%. Two prominent risk factors in the Moroccan population were highlighted: consanguinity, rate of which was significantly high at 30.8%, and previous maternal miscarriage or sibling sudden death, observed in 34.6% of cohort.

Conclusion: Impact of identified variants was discussed and possible disease-predisposing effect is suggested. Findings indicate that ASD may be favored by consanguineous marriage and that NKX2-5 variant rate in ASD patients may be affected by ethnicity. High level of maternal miscarriage and sibling sudden death suggests potential non-sporadic nature as result of putative genetic defect.

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Conflict of interest statement

Conflict of interest: None declared.

Figures

Figure 1
Figure 1
Sequencing chromatogram of the detected NKX2-5 variants, (a) Variant c.73C>T identified in patients P1, P2 and P3, (b) Variant c.114G>A identified in P 3, (c) Variant c.861C>T identified in P4, (d) organisation of NKX2-5 domains with exonic variants sites HD - homeodomain; TN - tinman domain
Figure 2
Figure 2
Multiple alignment of NKX2-5 protein sequences across species showing the R25 residue conservation among mammals
See this image and copyright information in PMC

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