Mutant Caveolin-3 Induces Persistent Late Sodium Current and Is Associated With Long-QT Syndrome
Key result
LQTS-associated mutant caveolin-3 increases late sodium current ~2- to 3-fold vs wild type.
- 2- to 3-fold increase
- n=905
Why the study?
Approximately 25% of congenital long-QT syndrome cases remain unexplained pathogenetically, motivating the search for novel LQTS-susceptibility genes such as caveolin-3 mutations.
Population
905 unrelated patients referred for LQTS genetic testing
Comparison
Mutant caveolin-3 vs wild-type caveolin-3
Design
Observational genetic and electrophysiological study with mutational analysis and heterologous expression
Authors
Discussion
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Member takes
Implication
Supports CAV3-related LQTS via late sodium current gain-of-function; animal data leave open clinical translation.
Study Design
Type
Observational (n=905)
Structured PICO
P
Population
905 unrelated patients referred for LQTS genetic testing, and HEK293 cells stably expressing the cardiac sodium channel hNav1.5
I
Intervention
Mutant caveolin-3 (CAV3 mutations)
C
Comparator
Wild-type caveolin-3
O
Outcome
Late sodium currentsurrogate
Main Result
Effect estimate: 2- to 3-fold increase
Mutations in CAV3 (caveolin-3) are associated with Long-QT syndrome by inducing a gain-of-function increase in late sodium current.
Cite This Study
Vatta et al. (2006) conducted an observational in Long-QT Syndrome (LQTS) (n=905). CAV3 mutations (mutant caveolin-3) vs. Wild-type caveolin-3 (control alleles) was evaluated on Late sodium current (2- to 3-fold increase). Mutant caveolin-3 identified in LQTS patients resulted in a 2- to 3-fold increase in late sodium current compared with wild-type caveolin-3.