Unraveling the ophthalmological phenotype and etiopathogenetic mechanisms in pseudoxanthoma elasticum (3F008414)
Pseudoxanthoma elasticum (PXE) is an autosomal recessive disorder, characterised by skin and eye symptoms, as well as heart and blood vessel (cardiovascular) disease, due to calcification of elastic fibres in these organs. It is caused by defects (mutation) in a transporter protein, ABCC6. Neither the substrate of this transporter, nor how it causes PXE is presently known. The first objective of this project is to get more insights into the mechanisms leading to calcification in PXE and in the major cellular events involved in this process.
Contrary to the skin and cardiovascular symptoms, the eye disease in PXE is less well studied. It has been suggested that the mechanisms leading to vision loss in PXE are unique and more complex than initially thought. Although visual problems are an important aspect in the diagnosis, treatment and counselling of PXE families, their natural history and pathogenesis is not well understood. Our second aim is to study the eye features in PXE patients using a comprehensive protocol in three patient cohorts.
The severity of PXE symptoms can be highly variable, between families or within one family. As no correlations with the ABCC6 mutations could be found, it is assumed that variants in other genes have an influence on the course of the disease (modifier genes). Our third objective is to identify modifiers for the cardiovascular and eye symptoms, which can be used in clinic to improve followup of patients and prevention of complications.