Clinical and Genetic Investigation of Atrial Septal Defect with Atrioventricular Conduction Defect in a Large Consanguineous Tunisian Family

BackgroundAtrial septal defect (ASD) is an autosomal dominant disease characterized by left-to-right shunting and increased right ventricular output. Approximately 5–10% of congenital heart diseases (CHD) are due to ASD, which is one of the most frequent CHD found in adults. The gene responsible for ASD was mapped to chromosome 5q35 encoding the transcription factor NKX2–5 that plays an important role for the regulation of septation during cardiac morphogenesis.MethodsA Tunisian family including four affected members was investigated. Individuals were genotyped using the polymorphic microsatellite markers D5S394 and D5S2069 overlapping the NKX2–5 gene.ResultsWe report here clinical and molecular investigation of a Tunisian consanguineous family with four affected members. Two presented with ASD associated with prolonged PR interval, whereas the other two presented only a prolonged PR interval. We also identified five asymptomatic individuals in the same family with ventricular preexcitation. Although the patients were products of a consanguineous marriage, no other abnormalities were observed in this family. Genotyping and linkage analysis showed exclusion of linkage between the gene responsible for ASD in this family and NKX2.5 gene.ConclusionsOur results further confirm the genetic heterogeneity of ASD.