Due to copyright issues, an electronic copy of the thesis must be ordered from the faculty. For the faculty to have time to process the order, the order must be received by the faculty at the latest 2 days before the public defence. Orders received later than 2 days before the defence will not be processed. After the public defence, please address any inquiries regarding the thesis to the candidate.
Trial Lecture – time and place
See Trial Lecture.
Adjudication committee
- First opponent: Professor Ruth Frikke-Schmidt, University of Copenhagen, Denmark
- Second opponent: Senior engineer Kristian Tveten, Telemark Hospital Trust, Norway
- Third member and chair of the evaluation committee: Professor II Arne Stray-Pedersen, University of Oslo
Chair of the Defence
Professor Bente Evy Halvorsen, University of Oslo
Principal Supervisor
Martin Prøven Bogsrud, Oslo University Hospital
Summary
This thesis is within the field of cardiovascular genetics and examines how genetic testing can improve the detection of individuals at risk for hereditary heart disease with a focus on diagnostic yield, clinical implications, and strategies for screening. The work summarizes more than 17 years of genetic testing for cardiomyopathies and arrhythmias in a national laboratory. Among patients tested between 2003 and 2020, likely pathogenic or pathogenic variants were found in 13.1% of patients with cardiomyopathy and 15.4% with arrhythmias, corresponding to 574 and 306 confirmed genetic diagnoses.
Cascade screening of relatives identified more than 2,500 additional carriers eligible for preventive follow-up. The estimated penetrance of disease among variant carriers was 30.6% for cardiomyopathies and 19.5% for arrhythmias. Reclassification of 54.2 % of the hypertrophic cardiomyopathy variants previously reported by our laboratory demonstrates the dynamic nature of variant interpretation and the need for continuous re-evaluation. A part of the thesis analyzed data from the Norwegian cascade screening program for familial hypercholesterolemia (FH) in children, demonstrating a considerable overlap in LDL-C levels between children with FH and children without FH, especially in newborns.
These findings indicate that cholesterol-based screening alone may fail to identify many affected children and highlight the value of genetic testing in early FH detection. Genetic testing showed higher sensitivity, and these results support FH as a stronger candidate for universal screening than cardiomyopathies and arrhythmias, where current knowledge limits screening to relatives of known patients.
Overall, the thesis emphasizes the importance of improving screening strategies for hereditary heart disease, and these results contribute to the knowledge needed to better identify individuals at risk.
Additional information
Contact the research support staff.