Clinical Phenotypes and ABCC6 Gene Mutations in Brazilian Families with Pseudoxanthoma Elasticum

Abstract

Pseudoxanthoma elasticum (PXE; OMIM 264800) manifests with characteristic skin lesions of yellowish papules which coalesce into plaques of inelastic and leathery skin on the predilection sites (1). The ocular findings consist of angioid streaks, choroidal neovascularization and subretinal hemorrhages resulting in loss of visual acuity and occasional blindness. Cardiovascular problems include hypertension, intermittent claudication, and occasional myocardial infarcts and stroke. The prevalence of PXE is estimated to be in the range of 1:50,000–70,000 and to be more frequent in females than in males. The diagnosis can be challenging to clinicians due to late-onset of clinical manifestations and considerable heterogeneity. PXE is associated with mutations in the ABCC6 gene which encodes a transmembrane efflux transporter expressed primarily in the liver and the kidneys (2). Consequently, PXE has been suggested to be a metabolic disorder with ectopic mineralization of the peripheral connective tissues. Recent studies have also suggested that cutaneous features of PXE can be found in patients with generalized arterial calcification of infancy due to mutations in the ENPP1 gene (3, 4). Previous studies, which have documented close to 600 distinct mutations in the ABCC6 gene, have suggested the presence of unique mutations affecting certain ethnic groups with different ancestral backgrounds (5, 6). In this study, we asked the specific question whether Brazilian patients of mixed European, Native Indian and African ancestry with PXE harbor unique ABCC6 mutations, and whether such mutations might be correlated with the clinical phenotypes in this population with particular reference to heterozygous carriers.