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

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 reaction- amplified 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 mis- carriage and sibling sudden death suggests potential non-sporadic nature as result of putative genetic defect. (Anatol J Cardiol 2017; 17: 217-23) Keywords: