Unraveling the Pathophysiological Mechanisms of Phospholamban R14del Cardiomyopathy: A Comprehensive Overview

Area of Science:

• Cardiovascular Genetics
• Molecular Cardiology
• Genetic Pathology

Background:

• The phospholamban R14del (p.Arg14del) mutation is a key genetic cause of inherited cardiomyopathies.
• This mutation affects phospholamban's regulation of the SERCA2a calcium pump in cardiomyocytes.
• PLN-R14del is linked to both dilated cardiomyopathy and arrhythmogenic cardiomyopathy.

Purpose of the Study:

• To systematically review and consolidate current literature on the PLN-R14del mutation.
• To elucidate the pathological phenotypes associated with PLN-R14del.
• To address unresolved questions regarding PLN-R14del cardiomyopathy pathogenesis and guide future research.

Main Methods:

• Systematic literature review of studies on the PLN-R14del mutation.
• Analysis of reported pathological phenotypes and clinical implications.
• Consolidation of existing knowledge and identification of research gaps.

Main Results:

• The PLN-R14del mutation has been identified in patients across 11 countries since 2006.
• PLN-R14del carriers frequently present with a combination of dilated and arrhythmogenic cardiomyopathy.
• The mutation contributes significantly to heart transplantations in some regions, e.g., the Netherlands.

Conclusions:

• Understanding the precise pathogenic mechanisms of PLN-R14del-induced heart disease requires further investigation.
• Consolidated knowledge on PLN-R14del cardiomyopathy aids in understanding its pathology.
• Future research should focus on advancing diagnostic and therapeutic strategies for individuals with PLN-R14del.