TY - JOUR
T1 - Tracing the pathogenic PLN p.(Arg14del) variant across the globe; more than just a local curiosity
AU - van Drie, Esmée
AU - van Lint, Freyja H M
AU - Zwart, Rob
AU - Wang, Jie
AU - Chen, Yucheng
AU - Postma, Alex V
AU - Elferink, Martin G
AU - van Steenbrugge, Joris J M
AU - van der Zwaag, Paul A
AU - Jongbloed, Jan D H
AU - Dooijes, Dennis
AU - van der Heide, Myrthe Y C
AU - Houweling, Arjan C
AU - Haugaa, Kristina H
AU - Leren, Ida Skrinde
AU - Kostareva, Anna
AU - Milting, Hendrik
AU - Nguyen, Thuy Vy
AU - Ho Huynh, Thuy Duong
AU - Chevalier, Philippe
AU - Delinière, Antoine
AU - Gimeno-Blanes, Juan R
AU - Sabater-Molina, María
AU - Barriales-Villa, Roberto
AU - Mazzanti, Andrea
AU - Memmi, Mirella
AU - Kuramoto, Yuki
AU - Tabata, Tomoka
AU - Wilde, Arthur A M
AU - van Spaendonck-Zwarts, Karin Y
AU - van Tintelen, J Peter
N1 - Publisher Copyright:
© The Author(s) 2026.
PY - 2026/6/25
Y1 - 2026/6/25
N2 - 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.
AB - 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.
KW - Calcium-Binding Proteins/genetics
KW - Cardiomyopathies/genetics
KW - Founder Effect
KW - Gene Frequency
KW - Genetic Predisposition to Disease
KW - Genetic Variation
KW - Global Health
KW - Haplotypes
KW - Heredity
KW - Humans
KW - Mutation
KW - Phenotype
KW - Phospholamban
KW - Prevalence
U2 - 10.1007/s12265-026-10792-6
DO - 10.1007/s12265-026-10792-6
M3 - Article
C2 - 42350697
SN - 1937-5387
VL - 19
JO - Journal of Cardiovascular Translational Research
JF - Journal of Cardiovascular Translational Research
IS - 1
M1 - 78
ER -