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A novel CSX/NKX2-5 mutation causes autosomal-dominant AV block: are atrial fibrillation and syncopes part of the phenotype?

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Gutierrez-Roelens, Ilse [UCL] De Roy, Lucas [UCL] Ovaert, Caroline [UCL] Sluysmans, Thierry [UCL] Devriendt, Koen Vikkula, Miikka [UCL]

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.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès restreint
Publication date 2006
Journal information "European Journal of Human Genetics" - Vol. 14, no. 12, p. 1313-1316 (2006)
Peer reviewed yes
Publisher Nature Publishing Group (London)
issn 1018-4813
e-issn 1476-5438
Publication status Publié
Affiliations UCL - MD/BICL - Département de biochimie et de biologie cellulaire
UCL - MD/GYPE - Département de gynécologie, d'obstétrique et de pédiatrie
UCL - MD/MINT - Département de médecine interne
UCL - (MGD) Service de cardiologie
UCL - (SLuc) Service de cardiologie pédiatrique
UCL - (SLuc) Centre de génétique médicale UCL
MESH Subject Female ; Heart Block - complications - physiopathology ; Heart Defects, Congenital - genetics - physiopathology ; Heart Septal Defects, Atrial - genetics ; Homeodomain Proteins - genetics ; Humans ; Male ; Mutation ; Pedigree ; Phenotype ; Transcription Factors - genetics
Keywords Septal defect ; Atrial fibrillation ; Heart ; AV block ; CSX/NKX2-5
Links
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Bibliographic reference Gutierrez-Roelens, Ilse ; De Roy, Lucas ; Ovaert, Caroline ; Sluysmans, Thierry ; Devriendt, Koen ; et. al. A novel CSX/NKX2-5 mutation causes autosomal-dominant AV block: are atrial fibrillation and syncopes part of the phenotype?. In: European Journal of Human Genetics, Vol. 14, no. 12, p. 1313-1316 (2006)
Permanent URL http://hdl.handle.net/2078.1/21950