A single nucleotide polymorphism in the Abcc6 gene associates with connective tissue mineralization in mice similar to targeted models for pseudoxanthoma elasticum

Pseudoxanthoma elasticum (PXE; OMIM#264800) is characterized by progressive, lateonset, ectopic mineralization of elastic fibers, clinically affecting skin, retina, and the cardiovascular system with considerable morbidity and occasional mortality (Neldner, 1988). It is an autosomal recessive disorder with a slight female preponderance and an estimated prevalence of ~1 in 50,000-70,000. The clinical diagnosis is usually made through recognition of characteristic skin lesions, i.e., small, yellow papules on flexural areas progressively coalescing into plaques of inelastic, leathery skin. The cutaneous findings are associated with angioid streaks in the retina and mineralization of arterial blood vessels. Adding to the diagnostic difficulty is the considerable phenotypic heterogeneity in age of onset and the extent and severity of organ system involvement. Since identification of mutations in the ATP binding cassette, subfamily C, member 6 gene (ABCC6) as the genetic basis in the overwhelming majority of families with PXE, tremendous progress has been made in understanding the molecular genetics, clinical phenotypes, and pathogenesis of this disease (Uitto et al., 2010).