To search for a genetic basis in a family with autosomal dominantly inherited atrial septal defect in combination with increasing conduction anomalies.

We searched for mutations in the NKX2.5 gene by sequencing of desoxyribonucleic acid in a previously investigated family.

All family members were included if they, after informed consent, had decided to participate in the genetic testing. A blood sample was sent from local doctors for analysis of potential mutations. Patients with cardiac anomalies were examined in our hospital. For those family members without cardiac anomalies, we relied on local information.

We identified the mutation Q149X in the NKX2.5 gene on chromosome 5q35 in all patients with atrial septal defect and disturbances of atrioventricular conduction. No family member without an atrial septal defect possessed the mutation, including a member with transposed arterial trunks.

We have identified a mutation in the NKX2.5 gene responsible for autosomal dominantly inherited atrial septal defect in the oval fossa combined with disturbances of atrioventricular conduction in 7 patients spanning 4 generations.