Pseudoxanthoma elasticum: evidence for the existence of a pseudogene highly homologous to the ABCC6 gene.

EDITOR—Pseudoxanthoma elasticum (PXE, MIM 264800) is an inherited disorder of connective tissue in which the elastic fibres of the skin, eyes, and cardiovascular system slowly become calcified, causing a spectrum of disease involving these three organ systems, with highly variable phenotypic expression. 2 Mutations in the ABCC6 gene (previously known as MRP6), encoding a 1503 amino acid membrane transporter, have recently been identified by our group and others as the genetic defect responsible for PXE. We subsequently designed a strategy for a complete mutational analysis of the ABCC6 gene, in order to provide accurate molecular and prenatal diagnosis of PXE. During this mutational screening, we have found evidence for the existence of at least one pseudogene highly homologous to the 5' end of ABCC6. Sequence variants in this ABCC6-like pseudogene could be mistaken for mutations in the ABCC6 gene and consequently lead to erroneous genotyping results in pedigrees aVected with pseudoxanthoma elasticum.