Mutations in a gene encoding an ABC transporter cause pseudoxanthoma elasticum

Pseudoxanthoma elasticum (PXE) is a heritable disorder characterized by cal cification of elastic fibres in skin, arteries and retina that results in d ermal lesions with associated laxity and loss of elasticity, arterial insuf ficiency and retinal haemorrhages leading to macular degefieration(1-5). PX E is usually found as a sporadic disorder, but examples of both autosomal r ecessive and autosomal dominant forms of PXE have been observed(6). Partial manifestations of the PXE phenotype have also been described in presumed c arriers in PXE families(7,8). Linkage of both dominant and recessive forms of PXE to a 5-cM domain on chromosome 16013.1 has been reported (refs 8,9). We have refined this locus to an 820-kb region containing 6 candidate gene s(10). Here we report the exclusion of five of these genes and the identifi cation of the first mutations responsible for the development of PXE in a g ene encoding a protein associated with multidrug resistance (ABCC6).