The KCNH2-IVS9-28A/G mutation causes aberrant isoform expression and hERG trafficking defect in cardiomyocytes derived from patients affected by Long QT Syndrome type 2

摘要

Background: Long QT Syndrome type 2 (LQT2) is caused bymutations in the KCNH2 gene that encodes for the alpha-subunit (hERG) of the ion channel conducting the rapid delayed rectifier potassium current (I-Kr). We have previously identified a disease causing mutation (IVS9-28A/G) in the branch point of the splicing of KCNH2 intron 9. However, the mechanism through which this mutation causes the disease is unknown.