Arrhythmias & electrophysiology
Genetic analysis identifies the SLC4A3 anion exchanger as a major gene for short QT syndrome
Authors' conclusion
In about a quarter of patients with SQTS, a potentially disease-causing variant can be identified. Nonsynonymous variants in SLC4A3 represent the most common cause of SQTS
Study context
- Population
- Index patients with short QT syndrome (SQTS)
- Participants
- 34 index patients
- Comparison
- SLC4A3 variant carriers vs Noncarriers
- SLC4A3 variant carriersn = 5
- Noncarriersn = 29reference
- Outcome
- Prevalence of potential disease-causing variants (gene panels including SLC4A3)
Methodological detailsmulticentre, zebrafish embryo heart model validation
- Multicentre
- Zebrafish embryo heart model validation
Performance
As reported in the abstract
Potentially disease-causing variants
- Any potentially disease-causing variant
- 9 (26%)
- Located in SLC4A3 (4 novel nonsynonymous: p.Arg600Cys, p.Arg621Trp, p.Glu852Asp, p.Arg952His; 1 known p.Arg370His)
- 15%
- KCNQ1
- 2×
- KCNJ2
- 1×
- CACNA1C
- 1×
Further findings
ECG intervals, SLC4A3 carriers vs noncarriers
- Similar heart rate but shorter QT and J point to T wave peak intervals in carriers
Zebrafish slc4a3 knockdown
- Shortened QTc (Bazett), rescued by native human AE3 but not by mutated variants p.Arg600Cys, p.Arg621Trp, p.Glu852Asp, p.Arg952His
- slc4a3/AE3 dysfunction associated with alkaline cytosol and shortened cardiomyocyte action potential
Original publication
Genetic analysis identifies the SLC4A3 anion exchanger as a major gene for short QT syndrome. Heart Rhythm. Published 15 February 2023. doi:10.
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