Abstract
The prevalence of congenital heart defects is approximately 1% of all live births. Identifying the genes responsible for cardiac malformation is the first step to understand pathogenesis. Heterozygous mutations in the CSX/NKX2-5 (NKX2E) gene have been identified to cause atrial septal defect (ASD) and/or atrioventricular (AV) conduction disturbance in some families. However, there is great variability in expressivity of the phenotype between the patients with a CSX/NKX2-5 mutation.
We screened four sporadic patients and three index cases of families with ASD and/or conduction defects. In one of them, a CSX/NKX2-5 mutation was identified. This novel mutation (p.Tyr256X) was inherited in a three-generation family causing five individuals to have cardiac anomalies ranging from ASD to arrhythmias. Interestingly, all the observed AV conduction disturbances were at the nodal level, manifesting first as an AV block of the first degree and evolving toward a second-degree block. Atrial fibrillation, previously reported in three individuals with CSX/NKX2-5 mutations, was observed in three patients.
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Acknowledgements
We are grateful to all the family members and patients for their invaluable contributions. These studies were supported by Interuniversity Attraction Poles initiated by the Belgian Science Policy, network 5/25 and the FNRS (Fonds national de la recherche scientifique) (to MV, a ‘Maître de recherche du FNRS’) and the National Foundation for Research in Pediatric Cardiology (to ThS.). I Gutierrez-Roelens was supported by a fellowship from FRIA (Fonds pour la formation à la recherche dans l'industrie et dans l'agriculture) and Patrimoine UCL. We thank Ms Anne Van Egeren for her expert technical assistance, and Ms Liliana Niculescu for secretarial help.
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Gutierrez-Roelens, I., Roy, L., Ovaert, C. et al. A novel CSX/NKX2-5 mutation causes autosomal-dominant AV block: are atrial fibrillation and syncopes part of the phenotype?. Eur J Hum Genet 14, 1313–1316 (2006). https://doi.org/10.1038/sj.ejhg.5201702
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DOI: https://doi.org/10.1038/sj.ejhg.5201702
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