A frameshift deletion in the sarcomere gene MYL4 causes early-onset familial atrial fibrillation
Authors' conclusion
Through a population approach we found a loss of function mutation in the myosin gene MYL4 that, in the homozygous state, is completely penetrant for early-onset AF.
Study context
- Population
- Icelanders8,453 whole genomes sequenced
- Participants
- 1,799 vs 337,453
- Comparison
- Early-onset atrial fibrillation (AF) cases vs controls
- Early-onset AFn = 1,799
- Controlsn = 337,453reference
- Outcome
- Sequence variants associated with early-onset AF
Methodological detailswhole-genome sequencing, case-control, population-based, recessive and multiplicative inheritance models
- Whole-genome sequencing, case-control
- Population-based
- Recessive and multiplicative inheritance models
Main finding
As reported in the abstract
Rare frameshift deletion in MYL4 (c.234delC) associated with early-onset AF, recessive mode
Allelic frequency of MYL4 c.234delC
0.58%
Homozygous carriers, all with early-onset AF
8
Homozygotes diagnosed by age 30
6
Homozygotes diagnosed in their 50s
2
Observational data: associations, not effects.
Further findings
Clinical events in homozygotes
- Pacemaker for sick sinus syndrome
- 3
- Ischemic stroke
- 3
- SCD
- 1
Original publication
A frameshift deletion in the sarcomere gene MYL4 causes early-onset familial atrial fibrillation. Eur Heart J. Published 14 October 2016. doi:10.
Summarised from the published abstract; every number is checked against it