T587M (Long QT syndrome)

- back to mutations table - KCNQ1 cartoon

FUNCTIONAL CHARACTERIZATION

This mutation was expressed by Yamashita et al in 2001. At variance with other C-term KCNQ1 mutations, T587M, was found in three independent probands that were clearly symptomatic with family history of cardiac sudden death. Functional assay using a heterologous expression system with a mammalian cell line (COS7 cells) revealed that the mutant displayed neither functional channels when expressed alone nor dominant-negative effect when co-expressed with wild-type (WT) KCNQ1. On confocal microscopic images, GFP-tagged the GFP-tagged mutant showed a perinuclear fluorescence pattern. Co-expression of the mutant with GFP-tagged WT KCNQ1 did not influence its normal cellular transport. Therefore, the T587M mutant cannot traffic to the plasma membrane and may form no subunit assembly with WT KCNQ1. Overal this mutation causes haploinsufficiency (50% current reduction).