G589D (LQT-1)
- back to mutations table -
KCNQ1 cartoon -
| Shift in V1/2 of activation | Shift in T1/2 of inactivation (-40mV) |
Current density | Expression System | Other | Reference |
|---|---|---|---|---|---|
| WT 11±2.2 mV |
WT 993±56ms |
COS | Reduced expression efficiency of mutant channels | Piippo et al 2001 | |
| GD 41.3±2.9 mV |
GD 995±54 mV |
-35%@0mV | co-exp. with KCNE1 | ||
| Positive | N.S |
N.S. : non different from WT
COMMENTS ON IN VITRO DATA
The G589D mutation has been initially identified in one JLN syndrome kindred.
Subsequent molecular screening led to the identification of G589D in 30% of
114 probands with RW syndrome, thus pointing to the hypothesis that this mutation
is responsible for a founder gene effect in the Finnish population. In vitro
expression of mutated channel showed a marked current reduction while the co-expression
with wild type did not modify significantly the expressed current. Interestingly
the expression efficiency of 598D protein was subnormal, since less than 20%
of the transfected cells displayed detectable current. In agreement with low
functional expression efficiency, NO DOMINANT NEGATIVE effect was observed.
Approximately 50% of the gene carriers had QTc<460 ms and 8% of the cardiac
events where associated with drug assumption (drug-induced Torsades de Pontes).
Taken together these results seem to provide further support to the hypothesis
that C-term mutations of KCNQ1 gene are associated with a mild phenotype.