Key result
KCNQ1 L251P mutation causes ~11-fold reduction in potassium current amplitude when coexpressed with wild-type KCNQ1.
Why the study?
Mutations causing congenital long QT syndrome have been identified in KCNQ1 potassium channel gene, but the biophysical characteristics of the new L251P mutation were unknown.
Population
CHO cells transfected with wild type or mutant KCNQ1 (L251P) with or without KCNE1
Comparison
Mutant KCNQ1 (L251P) expression vs wild type KCNQ1 expression
Design
Preclinical study using whole-cell patch clamp technique
Authors
Loading...
Supports L251P as cause of prolonged repolarization in LQTS; extends KCNQ1 mutation data from animal models but leaves clinical implications open.
Effect estimate: 11-fold reduction
The L251P mutation in the KCNQ1 channel exerts a dominant negative effect, drastically reducing potassium currents and explaining the prolonged repolarization seen in affected LQTS patients.
Deschênes et al. (2003) studied Long QT syndrome (LQTS). KCNQ1 (L251P) mutation vs. Wild type KCNQ1 was evaluated on Potassium current amplitude (11-fold reduction). The KCNQ1 (L251P) mutation produced no observable potassium current and caused an 11-fold reduction in current amplitude when coexpressed with wild-type KCNQ1.
Synapse has enriched 4 closely related papers on similar clinical questions. Consider them for comparative context: