Background: Cardiac arrhythmias are responsible for several cases of syncope and sudden cardiac death annually worldwide. Due to overlapping clinical symptoms in some cardiac arrhythmias genetic studies would help to confirm the primary clinical diagnosis made on the basis of solely clinical findings. In addition clinical management of the patient, family screening and provide appropriate counseling and risk assessment for the family members are other advantages of genetic study.
Materials and methods: Totally nine patients from a family included in this study. The primary diagnosis on the basis of clinical findings was second-degree atrioventricular (AV) block for this family. Mutation in SCN5A gene is frequently reported for second-degree AV block and hence the gene was analyzed using whole gene sequencing but no mutation was detected. Subsequently, the samples were subjected to customized Ampliseq 77 gene panel using next generation sequencing to detect the underlying molecular defects.
Results: We found c. 5570T>A missense mutation in ANK2 gene for this family. Based on the Online Mendelian Inheritance in Man, ANK2 gene and the mutation detected correspond to long QT syndrome type 4.
Conclusion: This mutation, although already known in other populations, but is reported for the first time in Iranian patients with cardiac arrhythmias. As the case with this family, genetic analysis of patients with cardiac arrhythmias would be helpful in reassessment of clinical diagnosis and therefore would help for patients' management and in some cases re-evaluation of ongoing treatment may be needed.
Keywords: Atrioventricular block; congenital long QT syndrome; hereditary cardiac arrhythmias; next generation sequencing.