Mutations in the desmoplakin (DSP) gene and arrhythmogenic right ventricular cardiomyopathy (ARVC)

The aim of this research project is to increase knowledge about mutations in the desmoplakin (DSP) gene. Mutations in the desmoplakin (DSP) gene have been associated with arrhythmogenic right ventricular cardiomyopathy (ARVC), which may lead to the development of heart failure and life-threatening cardiac rhythm disturbances. We want to uncover whether findings from echocardiography can indicate the risk of disease progression and whether individual patients should take specific precautions to prevent rapid disease development, severe illness, and death. We will particularly examine whether physical activity and pregnancy are risk factors in patients with DSP mutations.

Cardiomyopathies are defined as structural or functional heart muscle diseases in the absence of coronary artery disease, hypertension, valve defects, congenital heart diseases, or other underlying diseases. Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy that can lead to the development of heart failure and life-threatening cardiac rhythm disturbances. The disease is characterized by the replacement of normal myocardium with fibrous tissue and fatty tissue, with the right ventricle being particularly affected. The main cause of ARVC is mutations (genetic defects) in genes that encode for desmosomes. Desmosomes are central to the interaction and connection between heart muscle cells. Different genes can be affected, with mutations in the plakophilin-2 (PKP2) gene being the most common. In up to 40% of patients, no genetic mutation is detected, but this is likely due to many undiscovered mutations.

ARVC can debut at any age but is a frequent cause of sudden cardiac death in young individuals. This means that it is important to identify these patients so that measures to prevent disease progression and death can be implemented early on. It is also important to have knowledge of the factors that drive and exacerbate disease progression. The significance of different genetic defects is largely unknown, and identifying whether certain mutations carry a higher risk of severe disease development will be of great interest. Mutations in the desmoplakin (DSP) gene have been shown to be associated with 1-13% of ARVC cases. However, knowledge about this genetic mutation is limited, and there is a significant need for more studies in this area.

The results of the research project could impact the follow-up of these patients, especially in terms of informing and advising patients about physical activity and pregnancy. Furthermore, the results could indicate whether echocardiographic findings in individual patients can be linked to an increased risk of severe disease development, therefore supporting closer follow-up or early initiation of preventive treatment.

Researchers involved:

Paul Andre Sletten Olsen

Last updated 7/12/2024