PhD C.W.B. (Claudine) Ruijmbeek

Below is a brief summary of the dissertation:

Cardiomyopathy is a disease of the myocardium, involving cellular and structural alterations that affect the heart its ability to contract and to pump blood efficiently. It represents a heterogenous group of conditions with diverse clinical presentations and underlying genetic etiologies. Disease-causing variants have been identified in over 100 genes, encoding for proteins playing diverse roles within the cardiomyocyte. However, despite these insights, diagnostic yield in genetic testing remains low, leaving many patients worldwide classified as idiopathic. This suggests the presence of yet undiscovered genetic variants and disease mechanisms, and underscores the need for further research. Also, the pathogenic mechanisms by which numerous established disease-causing variants lead to clinical manifestations remain incompletely understood. When left untreated, cardiomyopathy can cause serious complications such as arrhythmias, heart failure, and sudden cardiac death. To improve outcomes for patients with genetic cardiomyopathy, we need to develop personalized treatment strategies that tackle the root cause of the disease. To accomplish this, we need to deepen our understanding of the genetic factors and disease mechanisms involved. This includes the discovery of new genetic causes and refining how genetic variants lead to and correlate with clinical manifestations. These insights will enable clinicians to establish more accurate diagnosis and risk prediction contributing to better patient care, and can ultimately drive the development of efficient targeted therapeutics. This thesis addresses these challenges and provides valuable insights into both the molecular and clinical aspects of genetic cardiomyopathy..