Tracing the pathogenic PLN p.(Arg14del) variant across the globe; more than just a local curiosity
Studying the global distribution of the pathogenic variant c.40_42delAGA;p.(Arg14del) in the phospholamban (PLN) gene is highly important for raising awareness among healthcare providers and may help uncover factors contributing to variability in the development of associated cardiomyopathy phenotypes. PLN p.(Arg14del)-positive individuals were identified through a PubMed literature search, our clinical and research networks, and ClinVar. Additionally, population prevalences were determined using publicly available genetic databases. Furthermore, haplotype analysis was conducted using haplotype markers or whole genome sequencing data to assess whether newly identified cases across different continents share common ancestry. The PLN p.(Arg14del) variant was identified in 21 countries across four continents. Haplotype marker analysis suggest that most analyzed individuals, except those from Greece, shared at least part of a common haplotype. The PLN p.(Arg14del) variant is present in at least 2000 carriers globally. While the majority share at least part of a common haplotype, suggesting a common founder, data suggest an independent mutational event in Greek patients.
Authors
- Arthur A.M. Wilde (ORCID: https://orcid.org/0000-0002-0528-0852)
- Mirella Memmi (ORCID: https://orcid.org/0000-0003-4006-5661)
- Yuki Kuramoto (ORCID: https://orcid.org/0000-0001-7368-3584)
- Freyja H.M. van Lint (ORCID: https://orcid.org/0000-0002-1787-4519)
- M Heide (ORCID: https://orcid.org/0009-0009-0251-7760)
- Dennis Dooijes (ORCID: https://orcid.org/0000-0003-0312-5354)
- Antoine Delinière (ORCID: https://orcid.org/0000-0002-3742-9674)
- Jan D.H. Jongbloed (ORCID: https://orcid.org/0000-0003-0663-404X)
- Paul A. van der Zwaag (ORCID: https://orcid.org/0000-0001-6693-0321)
- Andrea Mazzanti (ORCID: https://orcid.org/0000-0002-0208-2172)
- Ida S. Leren (ORCID: https://orcid.org/0000-0002-2716-9178)
- Tomoka Tabata
- Alex V. Postma (ORCID: https://orcid.org/0000-0003-4874-2487)
- Esmée van Drie (ORCID: https://orcid.org/0000-0002-6278-0626)
- Thuy Duong Ho Huynh (ORCID: https://orcid.org/0000-0001-8349-5624)
- Yi-Xiang Wang (ORCID: https://orcid.org/0000-0002-5246-5497)
- Rob Zwart
- Roberto Barriales-Villa
- Joris J.M. van Steenbrugge
- María Sabater-Molina
- Anna Kostareva
- Juan R. Gimeno-Blanes
- J. Peter van Tintelen (ORCID: https://orcid.org/0000-0003-3854-6749)
- Yucheng Chen
- Philippe Chevalier
- Martin G. Elferink
- Kristina H. Haugaa
- Hendrik Milting
- Thuy Vy Nguyen
- Arjan C. Houweling
- Karin Y. van Spaendonck-Zwarts
Institutions
- Université Claude Bernard Lyon 1 (FR)
- Vietnam National University Ho Chi Minh City (VN)
- Oslo University Hospital (NO)
- University Medical Center Groningen (NL)
- Radboud University Nijmegen (NL)
- University of Oslo (NO)
- Utrecht University (NL)
- Sichuan University (CN)
- University of Pavia (IT)
- Heart and Diabetes Center North Rhine-Westphalia (DE)
- Radboud University Medical Center (NL)
- Karolinska Institutet (SE)
- University Medical Center Utrecht (NL)
- West China Hospital of Sichuan University (CN)
- Hospices Civils de Lyon (FR)
- Netherlands Heart Institute (NL)
- Complexo Hospitalario Universitario A Coruña (ES)
- Hospital Universitario Virgen de la Arrixaca (ES)
- Amsterdam University Medical Centers (NL)
- Instituto de Investigación Biomédica de A Coruña (ES)
- University of Amsterdam (NL)
- The University of Osaka (JP)
Publication Details
- Journal
- Journal of Cardiovascular Translational Research
- Published
- 2026-06-25
- DOI
- https://doi.org/10.1007/s12265-026-10792-6
- Primary Topic
- Glycogen Storage Diseases and Myoclonus
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Foundation for Cardiovascular Research
- Fondation Leducq