title: Novel Clinical Manifestation of the Known SCN5A D1790G Mutation.
abstract: The D1790G mutation was found in all 24 patients of an extended long QT family but not in 200 chromosomes carried by healthy individuals. We describe a 37-year-old man presenting with a typical spontaneous type 1 Brugada pattern who in electrophysiological testing had easily inducible ventricular fibrillation. At the age of 47 years he had an atrial ventricular type 2 block documented by an exercise test and a Holter monitor. Genetic analysis revealed a known D1790G mutation in the gene encoding of the sodium channel (SCN5A) that until now has been associated only with the long QT phenotype. Although this mutation has not been associated with a reduction of sodium channel expression, we hypothesize that sodium currents are further diminished due to the 20-mV shift of the steady-state inactivation curve, and this could contribute to the Brugada phenotype. This case is important as it allows a better understanding of the underlying molecular mechanisms of Brugada syndrome. Moreover, this observation raises concern about the safety of class IC drug therapy in long QT type 3 patients and quinidine therapy in Brugada patients, and emphasizes the importance of a thorough clinical and genetic evaluation.
authors: Division of Pacing and Electrophysiology, Rambam Health Care Campus, Haifa, Israel.
authors: Miry
authors: M
authors: Blich
authors: Edna
authors: E
authors: Efrati
authors: Ibrahim
authors: I
authors: Marai
authors: Mahmoud
authors: M
authors: Suleiman
authors: Lior
authors: L
authors: Gepstein
authors: Monther
authors: M
authors: Boulous
mesh_terms: D053840:Brugada Syndrome / Q000235:genetics*; D000075224:Cardiac Conduction System Disease; D015716:Electrocardiography, Ambulatory; D005820:Genetic Testing; D006801:Humans; D008133:Long QT Syndrome / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000235:genetics*; D012964:Sodium / Q000097:blood
chemical_list: D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; D012964:Sodium