PHENOTYPICAL OVERLAPPING OF SICK SINUS ANDBRUGADA SYNDROMES IN A FAMILY WITH A NOVELSCN5A MUTATION

摘要

Mutation in SCN5A gene, encoding alpha-subunit of cardiac Na channels, causes a disease category called Na channelopathy. It has been noted to produce overlapping phenotypes such as long QT and Brugada syndromes (BS). We experience a case having a novel SCN5A mutation that was supposed to generate the phenotypes of sick sinus (SS) and BS. Sixty-eight-year-old male who had received a permanent pacemaker because of SSS at age 57 was admitted because of unexplained syncope. He has a strong family history of SSS and sudden death. Intravenous pilsicainide infusion (0.5mg/kg) unmasked typical ECG features of BS, and programmed RV outflow stimulation could produce ventricular fibrillation repeatedly. Genetic screening for SCN5A identified an abnormal conformer in exon 27 of the patient and his elderly brother. DNA sequencing revealed that both of them contained an insertion of two nucleotides, aa at 4729. Analysis of 110 normal control individuals did not identify the same mutation. This frame-shift mutation may cause non-functional Na channels because of stop codon insertion. To our knowledge this is a first case report of overlapping SS and BS caused by a unique SCN5A.