A mutation in the Phospholamban gene where the Arginine at position 14 (PLN-R14Del) is missing is causing a severe cardiomyopathy often leading to cardiac transplantation in the Netherlands. We estimated that approximately 25% of all transplanted patients carry this mutation. The origin is dated somewhere around the year 1300 in the north of country. Currently we have identified 1600 carriers with the identical mutation. We are in the process of developing and applying gene therapy to come to a specific treatment for the 700 carriers with symptoms we see today.
Download full-text PDF |
Source |
|---|
Publication Analysis
Top Keywords
Similar Publications
Hypertrophic cardiomyopathy: insights into pathophysiology and novel therapeutic strategies from clinical studies.
Egypt Heart J
January 2025
Department of Physiology, Faculty of Basic Medical Sciences, Obafemi Awolowo College of Health Sciences, Olabisi Onabanjo University, Sagamu Campus, Sagamu, Ogun State, Nigeria.
Background: Hypertrophic cardiomyopathy (HCM) is a frequently encountered cardiac condition worldwide, often inherited, and characterized by intricate phenotypic and genetic manifestations. The natural progression of HCM is diverse, largely due to mutations in the contractile and relaxation proteins of the heart. These mutations disrupt the normal structure and functioning of the heart muscle, particularly affecting genes that encode proteins involved in the contraction and relaxation of cardiac muscle.
View Article and Find Full Text PDFFrom Ca dysregulation to heart failure: β-adrenoceptor activation by RKIP postpones molecular damages and subsequent cardiac dysfunction in mice carrying mutant PLN by correction of aberrant Ca-handling.
Pharmacol Res
January 2025
Institute of Pharmacology and Toxicology, University of Würzburg, Versbacher Str. 9, Würzburg 97078, Germany; Leibniz-Institut für Analytische Wissenschaften - ISAS - e.V., Bunsen-Kirchhoff-Str. 11, Dortmund 44139, Germany; Comprehensive Heart Failure Center, University Hospital of Würzburg, Am Schwarzenberg 15, Würzburg 97078, Germany. Electronic address:
Article Synopsis
- Impaired calcium (Ca) handling in heart cells is a key feature of heart failure (HF), leading to issues like weakened heart contractions and irregular heartbeats.
- The study used transgenic mice with a mutation affecting a calcium regulator (phospholamban) to understand how defects in calcium cycling contribute to HF, noting that these mice experience severe and fast-progressing heart failure.
- Early treatment aimed at correcting calcium cycling using Raf kinase inhibitor protein (RKIP) was found to delay heart cell damage and improve overall health of the mice, indicating that addressing Ca dynamics early on could be crucial for preventing further complications in heart failure.
Dilated cardiomyopathy variant R14del increases phospholamban pentamer stability, blunting dynamic regulation of calcium.
J Biol Chem
December 2024
Department of Cell and Molecular Physiology, Loyola University Chicago, Maywood, Illinois, USA. Electronic address:
The sarco(endo)plasmic reticulum Ca ATPase (SERCA) is a membrane transporter that creates and maintains intracellular Ca stores. In the heart, SERCA is regulated by an inhibitory interaction with the monomeric form of the transmembrane micropeptide phospholamban (PLB). PLB also forms avid homo-pentamers, and the dynamic exchange of PLB between pentamers and SERCA is an important determinant of cardiac responsiveness to exercise.
View Article and Find Full Text PDFCardiac Applications of CRISPR/AAV-Mediated Precise Genome Editing.
bioRxiv
December 2024
Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
The ability to efficiently make precise genome edits in somatic tissues will have profound implications for gene therapy and basic science. CRISPR/Cas9 mediated homology-directed repair (HDR) is one approach that is commonly used to achieve precise and efficient editing in cultured cells. Previously, we developed a platform capable of delivering CRISPR/Cas9 gRNAs and donor templates via adeno-associated virus to induce HDR (CASAAV-HDR).
View Article and Find Full Text PDFHomozygous Phospholamban Mutation Causing Dilated Cardiomyopathy in a Young Man: From Cardiogenic Shock to Tennis Tournaments.
Clin Transplant
November 2024
Cardiac Surgery Unit, Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari Medical School, Bari, Italy.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!