What question did this study set out to answer?

To identify and functionally characterize novel gene mutations associated with the Brugada syndrome electrocardiogram phenotype.

April 22, 2009Circulation Cardiovascular Genetics

A Mutation in the β3 Subunit of the Cardiac Sodium Channel Associated With Brugada ECG Phenotype

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Population

A 64-year-old white male with type 1 ST-segment elevation in V1 and V2 during procainamide challenge, 296…

Comparison

Expression of SCN3B/L10P mutant gene vs Expression of wild-type SCN3B gene

Design

Preclinical

Authors

DHDan HuNorth Sichuan Medical University HBHéctor Barajas-MartínezElectrophysiology EBElena BurashnikovLankenau Institute for Medical Research

Discussion

Member takes

Implication

SCN3B L10P may underlie Brugada syndrome via sodium channel dysfunction; hypothesis-generating pending clinical cohort validation.

Key Points

To identify and functionally characterize novel gene mutations associated with the Brugada syndrome electrocardiogram phenotype.
Sequenced candidate genes using polymerase chain reaction in a 64-year-old male exhibiting type 1 ST-segment elevation after procainamide challenge and in 296 controls.
Coexpressed wild-type and mutant (SCN3B L10P) constructs with SCN5A and SCN1B in TSA201 cells to measure electrophysiological properties using whole-cell patch-clamp.
Assessed channel subcellular localization using confocal microscopy with green fluorescent protein tagging and verified protein presence via Western blot.
Identified a novel heterozygous SCN3B missense mutation (L10P) in exon 1 that was absent in 296 control alleles and known Brugada-associated genes.
Observed an 82.6% decrease in peak sodium current density, accelerated inactivation, slowed reactivation, and a -9.6-mV shift in half-inactivation voltage in SCN3B L10P coexpression compared to wild-type.
Found via confocal microscopy that SCN5A channels coexpressed with mutant SCN3B remained trapped in intracellular organelles rather than trafficking to the cell surface.

Structured PICO

Population

A 64-year-old white male with type 1 ST-segment elevation in V1 and V2 during procainamide challenge, 296 controls, and TSA201 cells for in vitro expression.

Intervention

Expression of SCN3B/L10P mutant gene

Comparator

Expression of wild-type SCN3B gene

Outcome

Peak sodium current density, channel kinetics (inactivation/reactivation), and cellular localization of the sodium channelsurrogate

Identifies a novel missense mutation (L10P) in the SCN3B gene that causes loss of function in the cardiac sodium channel, leading to a Brugada ECG phenotype.

Cite This Study

Hu et al. (2009) studied this question.

synapsesocial.com/papers/6a7c2aa6f92b625ceba1592e https://doi.org/10.1161/circgenetics.108.829192

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A Mutation in the β3 Subunit of the Cardiac Sodium Channel Associated With Brugada ECG Phenotype

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

A Mutation in the β3 Subunit of the Cardiac Sodium Channel Associated With Brugada ECG Phenotype

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Also Consider

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