Mutations in ABCC6 cause pseudoxanthoma elasticum

Pseudoxanthoma elasticum (PXE) is a heritable disorder of the connective tissue. PXE patients frequently experience visual field loss and skin lesions, and occasionally cardiovascular complication(1-4). Histopathological findings reveal calcification of the elastic fibres and abnormalities of the collagen fibrils(5). Most PXE patients are sporadic, but autosomal recessive and dominant inheritance are also observed(6,7). We previously localized the PXE gene to chromosome 16p13.1 (refs 8,9) and constructed a physical map(10). Here we describe homozygosity mapping in five PXE families and the detection of deletions or mutations in ABCC6 (formerly MRP6) associated with all genetic forms of PXE in seven patients or families.