Next generation sequencing in clinical practice Illustrated by studies in hereditary connective tissue disorders

The research in this thesis was performed at the department of human genetics of the Amsterdam UMC. At location AMC there is a long-standing history of care for patients with Marfan syndrome and related disorders. In addition, genetic testing for these disorders has been performed at the diagnostic laboratory of the VUmc for years. Combined, we were able to study both clinical and genetic data in a large patient cohort. This proved us with an excellent opportunity for clinical research, both in relatively large patient cohorts and in families with these connective tissue disorders.
In part 1, the outcomes and applications of next generation sequencing (NGS) in different hereditary connective tissue disorders (e.g. hereditary aortic disease and ectopia lentis) are illustrated by several cohort studies and/or literature studies. Based on the outcomes of genetic testing in cohort studies such as those described in part 1, guidelines on whom to offer these tests can be established. In part 2, the importance of raising awareness for genetic diseases is illustrated by several remarkable families with a hereditary connective tissue disorder. The presented cases highlight the clinical value of genetic testing in diagnosing hereditary aortic disease and the opportunities provided by the rapid advances in the field of human genetics.