title: A novel CSX/NKX2-5 mutation causes autosomal-dominant AV block: are atrial fibrillation and syncopes part of the phenotype?
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.
authors.affiliation: Laboratory of Human Molecular Genetics, Christian de Duve Institute of Cellular Pathology and Université catholique de Louvain, Avenue Hippocrate 74+5, bp 75.39, B-1200 Brussels, Belgium.
authors.forename: Ilse
authors.initials: I
authors.lastname: Gutierrez-Roelens
authors.forename: Luc
authors.initials: L
authors.lastname: De Roy
authors.forename: Caroline
authors.initials: C
authors.lastname: Ovaert
authors.forename: Thierry
authors.initials: T
authors.lastname: Sluysmans
authors.forename: Koen
authors.initials: K
authors.lastname: Devriendt
authors.forename: Han G
authors.initials: HG
authors.lastname: Brunner
authors.forename: Miikka
authors.initials: M
authors.lastname: Vikkula
mesh_terms: D005260:Female; D006327:Heart Block / Q000150:complications* / Q000503:physiopathology; D006330:Heart Defects, Congenital / Q000235:genetics* / Q000503:physiopathology; D006344:Heart Septal Defects, Atrial / Q000235:genetics; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; C095552:NKX2-5 protein, human; D014157:Transcription Factors