Expression defect of the rare variant/Brugada mutation R1512W depends upon the SCN5A splice variant background and can be rescued by mexiletine and the common polymorphism H558R.

Abstract excerpt

Background : Mutations in SCN5A that decrease Na current underlie arrhythmia syndromes such as the Brugada syndrome (BrS). SCN5A in humans has two splice variants, one lacking a glutamine at position 1077 (Q1077del) and one containing Q1077. We investigated the effect of splice variant background on loss-of-function and rescue for R1512W, a mutation reported to cause BrS. Methods and results : We made the...

Topics

• Humans
• NAV1.5 Voltage-Gated Sodium Channel
• HEK293 Cells
• Mexiletine
• Brugada Syndrome
• Mutation
• Polymorphism, Genetic