Heart failure & cardiomyopathies
Disease penetrance and phenotypic spectrum of desmoplakin variant carriers in the population
Authors' conclusion
DSP pDel variants are common but show low penetrance for myocarditis and cardiomyopathy, with risk increasing with more stringent classification.
Study context
- Population
- UK Biobank participants with exome sequencingUK Biobank
- Participants
- 200,580 participants
- Exposure
- Desmoplakin (DSP) variant carriers vs genotype-negative controls
- Predicted deleterious (pDel)n = 1,407
- Predicted loss of function (pLOF)n = 168
- P/LPn = 44
- Outcome
- Prevalence and phenotypic penetrance of DSP variants
Methodological detailspopulation-based, genotype-first, UK Biobank exome sequencing
- Population-based
- Genotype-first
- UK Biobank exome sequencing
Main finding
As reported in the abstract
Myocarditis and cardiomyopathy by DSP variant class
Myocarditis
Cardiomyopathy
| Outcome | pDel | pLOF | P/LP | Controls |
|---|---|---|---|---|
| Carrier prevalence | 0.7% | 0.08% | 0.02% | — not stated in the abstract |
— not stated in the abstract
Observational data: associations, not effects.
Further findings
Electrocardiographic (ECG) and CMR findings (subset of pDel carriers vs matched controls)
- More frequent lateral T-wave inversions and abnormal LV strain in DSP carriers
Variant clustering
- Missense variants clustered within 2 functional DSP domains
Original publication
Disease penetrance and phenotypic spectrum of desmoplakin variant carriers in the population. Heart Rhythm. Published 21 October 2025. doi:10.
Composed by AI from the published abstract and checked against it. How Briefs are made →