PhD ceremony Ms. K.Y. van Spaendonck-Zwarts: Inherited cardiomyopathies; genetics and gene-environment interactions

PhD ceremony: Ms. K.Y. van Spaendonck-Zwarts

Dissertation: Inherited cardiomyopathies; genetics and gene-environment interactions

Promotor(s): prof. I.M. van Langen, prof. M.P. van den Berg

Faculty: Medical Sciences

In the last two decades there have been important breakthroughs in unraveling the genetic factors underlying inherited heart muscle diseases (cardiomyopathies). This is especially important for the relatives of patients with cardiomyopathies. Timely diagnosis of cardiomyopathies and identifying individuals at risk, provide the possibility of preventing complications and reducing morbidity and mortality. This thesis focuses mainly on cardiomyopathy with dilatation (dilated cardiomyopathy, or DCM).

The first part of the thesis presents genetic causes and characterization of involved features or signs. Several Dutch founder mutations (mutations that emerged in a population many generations ago and that have subsequently spread among following generations) are discussed.

The second part of this thesis presents two hitherto unknown gene-environment interactions in inherited cardiomyopathies: pregnancy and chemotherapy. An important discovery that is described is that a subset of cases with pregnancy-related cardiomyopathy is hereditary, whereas previously it was thought that this type of cardioyopathy was non-genetic and non-familial. This discovery is supported by the identification of mutations in the largest human gene, the Titin gene. Full and larger scale analysis of this enormous large gene became only recently available (by new genomic techniques).