Tracing the pathogenic PLN p.(Arg14del) variant across the globe; more than just a local curiosity

Abstract

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.