Heart failure & cardiomyopathies
Natural Missplicing Events Amplified by an Elusive Deep-Intronic MYBPC3 Variant Cause Hypertrophic Cardiomyopathy
Authors' conclusion
MYBPC3 c.2308+227G>A is a pathogenic splice-altering variant that causes HCM by amplifying natural missplicing events.
Study context
- Population
- Genotype-negative patients with hypertrophic cardiomyopathy (HCM) from Salamanca, Spain, and their relatives35 probands · 46 relatives
- Participants
- 81 patients
- Outcome
- Pathogenicity of deep-intronic variant MYBPC3 c.2308+227G>A
Methodological detailsfamily cosegregation, splicing assays, haplotype reconstruction
- Family cosegregation
- Splicing assays
- Haplotype reconstruction
Main finding
As reported in the abstract
Carriers meeting HCM diagnostic criteria
56
69%
Cumulative penetrance by age 60 y, women
81%
Cumulative penetrance by age 60 y, men
96%
Combined LOD score across 20 informative families (strong evidence of cosegregation)
5.51
Further findings
HF, arrhythmic events, AF, mortality in probands vs carriers of other pathogenic MYBPC3 variants · follow-up
- No significant differences
Original publication
Natural Missplicing Events Amplified by an Elusive Deep-Intronic MYBPC3 Variant Cause Hypertrophic Cardiomyopathy. Circulation. Published 15 September 2026. doi:10.
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