Sick sinus syndrome (SSS), atrial fibrillation (AF) and atrioventricular nodal reentry tachycardia (AVNRT) are types of cardiac arrhythmia which is characterized by the abnormal electrical activity that causes an irregular heart beat. Previous studies have shown that cardiac disorders such as arrhythmia have been associated with mutations in voltage-gated ion channels. The purpose of the study is to understand that mutations in voltage-gated ion channels can cause electrical disturbances to the channel, thus explain the correlation with cardiac arrhythmia.

Two unrelated families with SSS and AF/AVNRT were studied. DNA was extracted from buccal cells and sequencing analysis was performed for four candidate genes: SCN5A, RYR2, KCNQ1 and LMNA. The sequencing results showed that there were no mutations that may explain the disease phenotypes; however, a number of single nucleotide polymorphisms (SNP’s) were found. Both probands of the families were found to have a change in the SCN5A gene (1867A>G; p.His558Arg). This SNP was further studied as a possible genetic modifier effect due to consanguinity; however, it did not track with the disease phenotype in other affected family members.

Our study did not identify a disease-causing mutation in the candidate genes. Possible explanations include: mutation in other voltage or non-voltage gated-ion channel genes which can cause various cardiac disorders including arrhythmia. A new genome-wide sequencing analysis coupled with bioinformatics may be used to identify many of the mutations that are associated with these types of disorders. When equipped with the right tools for data interpretation and communication with patients, these new approaches may work as effectively as many of their predecessors did in a clinical setting.