The Turkish Journal of Pediatrics 2017 , Vol 59 , Num 5
Novel NKX2-5 germline mutation in a Moroccan child with transitional atrio-ventricular septal defect (tAVSD)
Ihssane El-Bouchikhi 1-2 ,Khadija Belhassan 1 ,Fatima Zohra Moufid 1-2 ,Mohammed Iraqui Houssaini 2 ,Karim Ouldim 1 ,Samir Atmani 3
1 Medical Genetics and Oncogenetics Laboratory, Hassan II University Hospital, Fez, Morocco
2 Laboratory of Microbial Biotechnology, Faculty of Sciences and Techniques, University of Sidi Mohammed Ben Abdellah, Fez, Morocco
3 Medico-Surgical Unit of Cardio-pediatrics, Department of Pediatrics, Hassan II University Hospital, Fez, Morocco;
DOI : 10.24953/turkjped.2017.05.019 El-Bouchikhi I, Belhassan K, Moufid FZ, Houssaini MI, Ouldim K, Atmani S. Novel NKX2-5 germline mutation in a Moroccan child with transitional atrio-ventricular septal defect (tAVSD). Turk J Pediatr 2017; 59: 610-613.

Atrioventricular septal defect is a complex congenital heart defects (CHD) with a prevalence of approximately 4% of all CHDs. Transitional form of atrio-ventricular septal defect (tAVSD) associates ostium primum atrial septal defect, common atrioventricular annulus with distinct atrioventricular valvar orifices in addition of restrictive ventricular septal defect. We describe in this report clinical and molecular features of a Moroccan boy that carries a novel NK2 homeobox 5 (NKX2-5) germline mutation (Pro141Ala), and exhibits a transitional atrio-ventricular septal defect. This phenotype has never been reported in association with NKX2-5 germline mutations. Pro141Ala is a non-reported pathogenic mutation that alters the nuclear localization signal sequence, leading to disruption of NKX2-5 nuclear translocation mechanism. Such alteration would decrease nuclear transcriptional activity of NKX2-5 and impair cardiogenesis process. The present report comes to widen the phenotypic spectrum of congenital heart disease caused by NKX2-5 germline mutations, and highlights as well the importance of the nuclear localization system in NKX2-5 activity. Keywords : atrio-ventricular septal defect (AVSD), NKX2-5, nuclear localization site (NLS)

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