Patients with premature coronary artery disease who carry the ABCC6 R1141X mutation have no Pseudoxanthoma Elasticum phenotype

Background Pseudoxanthoma elasticum (PXE) is an inherited disorder of elastic tissue. We recently found that heterozygosity for the frequent (0.8% prevalence in Dutch population) R1141X mutation in the PXE gene coding for the ABCC6 transporter, is associated with a fourfold risk of premature coronary artery disease. Yet, it is not clear whether or not heterozygosity for this mutation results in a mild PXE phenotype. The objective of our study was to determine if skin and/or eye abnormalities related to a PXE phenotype could be found in patients with premature coronary artery disease, with and without the R1141X mutation. Methods R1141X mutation carriers with premature coronary artery disease (cases) and patients with premature coronary artery disease with no–or not known–mutation (controls) were studied. Cases and controls were examined for PXE-like skin changes and retinal angioid streaks, peau dʹorange or pigment epithelium changes. Results 7 cases and 31 controls were analysed. In both the mutation-positive and the control group, skin inspection and eye fundus examination did not reveal any dermatological or ocular signs of PXE. Conclusions Carriers for the ABCC6 R1141X mutation, which is frequent and confers a high risk of premature coronary artery disease, do not commonly have skin or eye abnormalities consistent with a mild PXE phenotype.