Diversity in disease course of Duchenne and Becker muscular dystrophy

Bergen, J.C. van den (2015)

Doctoral Thesis

In this thesis research is presented about the progressive muscle diseases Duchenne and Becker muscular dystrophy, two hereditary muscle diseases caused by a mutation in the gene coding for dystrophin, a protein involved in muscle membrane stability. The first part describes the disease course of both diseases. It evaluates the effect of developments in care of Duchenne patients, improving age at wheelchair dependence and survival. Data are presented about the relatively mild disease course of selected Becker patients with a mutation that would be the result of exon skipping in a Duchenne patient, illustrating the possible result of this therapeutic approach. The second part of this thesis focusses on research into factors involved in disease variability. Data are presented regarding the role of dystrophin quantity in disease severity in Becker patients, showing no linear relationship. Expression of several dystrophin associated proteins is shown not to influence disease course either. Contrarily, a single nucleotide polymorphism in the LTBP4 gene involved in fibrosis and muscle regeneration is shown to influence disease severity. Lastly, a disease severity scale for Becker patients is presented in this thesis, enabling a better comparison of individual patients for the purpose of scientific research.

• Disease severity
• Natural history
• Dystrophin
• Muscular dystrophy
• Scale
• Becker
• Duchenne

• All authors: Bergen, J.C. van den
• Supervisor: Verschuuren, J.J.G.M.
• Co-supervisor: Aartsma-Rus, A.M.
• Qualification: Doctor (dr.)
• Awarding Institution: Department of Neurology, Faculty of Medicine (LUMC), Leiden University
• Date: 2015-06-24
• ISBN (print): 9789462990821