Analysis of ABCC6: elucidation of the molecular pathology of pseudoxanthoma elasticum

Abstract

This thesis describes research to elucidate the molecular pathology of pseudoxanthoma elasticum (PXE), from phenotype to genotype. PXE is an autosomally inherited disorder of connective tissue, affecting the skin, Bruch's membrane of the eye, and cardiovascular system. The most apparent clinical features of PXE is the skin manifestation. Ocular features include angioid streaks, peau d'orange, and comet-like streaks in the retina. Disability in PXE is usually the result of vascular complications, among which loss of visual acuity due to hemorrhage and scarring in the centre of the retina, the macula lutea. PXE is either sporadic or usually segregates as an recessive disorder. Also dominant inheritance has been described. PXE is caused by mutations in the ABCC6 (ATP-binding cassette, subfamily C, member 6) gene encoding a transmembrane protein. The aim of this thesis was outlined in a brief introduction on PXE in chapter 1.1. The history of PXE was described in chapter 1.2 in which we summarized clinical, histopathological, and molecular aspects of PXE by reviewing the literature over the period from 1966 to 2002