Disease relevance of Pseudoxanthoma Elasticum

• In this review we are discussing the current status of the research on the elastin diseases with particular emphasis on clinical conditions affecting skin, as for example, cutis laxa, pseudoxanthoma elasticum, and the Buschke-Ollendorff syndrome [1].
• Analysis of sequence variations in the ABCC6 gene among patients with abdominal aortic aneurysm and pseudoxanthoma elasticum [2].
• Fluorescein angiography was found to be of potential value in the early recognition of angioid streaks and pseudoxanthoma elasticum [3].
• In humans, members of the ABC protein families A, B, C, D and G are mutated in a number of lipid transport and metabolism disorders, such as Tangier disease, Stargardt syndrome, progressive familial intrahepatic cholestasis, pseudoxanthoma elasticum, adrenoleukodystrophy or sitosterolemia [4].
• Moyamoya disease, fibromuscular dysplasia, hereditary hemorrhagic telangiectasia, hereditary cerebral hemorrhage with amyloidosis, pseudoxanthoma elasticum, two types of subcortical encephalopathy in Japan, HERNS and CADASIL are described [5].

High impact information on Pseudoxanthoma Elasticum

• Mutations in ABCC6 cause pseudoxanthoma elasticum [6].
• Mutations in a gene encoding an ABC transporter cause pseudoxanthoma elasticum [7].
• Pseudoxanthoma elasticum: mutations in the MRP6 gene encoding a transmembrane ATP-binding cassette (ABC) transporter [8].
• Disruption of Abcc6 in the mouse: novel insight in the pathogenesis of pseudoxanthoma elasticum [9].
• Pseudoxanthoma elasticum and rheumatoid arthritis [10].

Chemical compound and disease context of Pseudoxanthoma Elasticum

• The presenting symptoms may have resulted from the abnormal numbers and properties of elastic fibres, and the changes were caused by penicillamine use, rather than by idiopathic, inherited pseudoxanthoma elasticum [11].
• Hyaluronic acid and dermatan sulfate in non-lesional pseudoxanthoma elasticum skin [12].
• The role of fluorescein angiography in early diagnosis of lesions on fundus of the eye at pseudoxanthoma elasticum patients has been shown [13].
• Cysteine protease characteristics of the proteoglycanase activity from normal and pseudoxanthoma elasticum (PXE) fibroblasts [14].
• Pentoxifylline for ischemic pain in pseudoxanthoma elasticum [15].

Biological context of Pseudoxanthoma Elasticum

• Identification of ABCC6 pseudogenes on human chromosome 16p: implications for mutation detection in pseudoxanthoma elasticum [16].
• Multidrug resistance protein-6 (MRP6) in human dermal fibroblasts. Comparison between cells from normal subjects and from Pseudoxanthoma elasticum patients [17].
• Patients with premature coronary artery disease who carry the ABCC6 R1141X mutation have no Pseudoxanthoma Elasticum phenotype [18].
• It seems rational that defects in various extracellular matrix proteins cause lipoid proteinosis or subtypes of cutis laxa, yet the discovery of a liver- and kidney-based transmembrane transporter as the culprit of pseudoxanthoma elasticum was rather surprising and may shed new light on elastic tissue homeostasis [19].

Anatomical context of Pseudoxanthoma Elasticum

• Mutations in human multidrug resistance protein 6 (MRP6, ABCC6), a member of the MRP family of drug efflux pumps, are the genetic basis of Pseudoxanthoma elasticum, a disease that affects elastin fibers in the skin, retina, and blood vessels [20].
• Loss-of-function mutations of ABCC6 are associated with the development of pseudoxanthoma elasticum (PXE), a recessive hereditary disorder affecting the elastic tissues [21].
• Mutations in ABCC6 result in pseudoxanthoma elasticum, a multi-system heritable connective tissue disorder with variable phenotypic expression [22].
• In patients with pseudoxanthoma elasticum a thicker and more elastic carotid artery is associated with elastin fragmentation and proteoglycans accumulation [23].

Gene context of Pseudoxanthoma Elasticum

• Mutations in the ABCC6 (MRP6) gene cause pseudoxanthoma elasticum (PXE), a rare heritable disorder resulting in the calcification of elastic fibers [24].
• In a comprehensive mutational screening, we have analysed the entire coding region of the pM5, MRP1, and NPIP genes in 7 patients affected with pseudoxanthoma elasticum, but failed to find evidence of disease-causing defects in any of these three genes [25].
• Here, we report on a large Italian family affected by pseudoxanthoma elasticum for which linkage analysis had pointed to a region encompassing markers D16S3069-D16S405-D16S3103; hemizygosity of marker D16S405 allowed us to detect a submicroscopic deletion of at least 900 kb involving ABCC6, ABCC1, and MYH11 [26].
• Dermal fibroblasts from pseudoxanthoma elasticum patients have raised MMP-2 degradative potential [27].
• Elevated xylosyltransferase I activities in pseudoxanthoma elasticum (PXE) patients as a marker of stimulated proteoglycan biosynthesis [28].

Analytical, diagnostic and therapeutic context of Pseudoxanthoma Elasticum

• Stepwise logistic regression analysis did not reveal prognostic value in independent variables such as transfusions, chelation therapy, pseudoxanthoma elasticum skin lesions and/or angioid streaks, diabetes, hemoglobin, serum ferritin, and uric acid [29].

References