Pseudoxanthoma elasticum: a clinical, histopathological, and molecular update.
Pseudoxanthoma elasticum is an autosomally inherited disorder that is associated with the accumulation of mineralized and fragmented elastic fibers in the skin, Bruch's membrane in the retina, and vessel walls. The ophthalmic and dermatologic expression of pseudoxanthoma elasticum and its vascular complications are heterogeneous, with considerable variation in phenotype, progression, and mode of inheritance. Using linkage analysis and mutation detection techniques, mutations in the ABCC6 gene were recently implicated in the etiology of pseudoxanthoma elasticum. ABCC6 encodes the sixth member of the ATP-binding cassette transporter and multidrug resistance protein family (MRP6). In humans, this transmembrane protein is highly expressed in the liver and kidney. Lower expression was found in tissues affected by pseudoxanthoma elasticum, including skin, retina, and vessel walls. So far, the substrates transported by the ABCC6 protein and its physiological role in the etiology of pseudoxanthoma elasticum are not known. A functional transport study of rat MRP6 suggests that small peptides such as the endothelin receptor antagonist BQ123 are transported by MRP6. Similar molecules transported by ABCC6 in humans may be essential for extracellular matrix deposition or turnover of connective tissue at specific sites in the body. One of these sites is Bruch's membrane. This review is an update on etiology of pseudoxanthoma elasticum, including its clinical and genetic features, pathogenesis, and biomolecular basis.
Hu
Xiaofeng
X
Department of Ophthalmogenetics, The Netherlands Ophthalmic Research Institute, KNAW, Amsterdam, The Netherlands.
Plomp
Astrid S
AS
van Soest
Simone
S
Wijnholds
Jan
J
de Jong
Paulus T V M
PT
Bergen
Arthur A B
AA
D000818:Animals; D006801:Humans; D008967:Molecular Biology; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D009154:Mutation; D011561:Pseudoxanthoma Elasticum / Q000235:genetics* / Q000473:pathology*; D012164:Retinal Diseases / Q000235:genetics / Q000473:pathology
D027425:ATP-Binding Cassette, Sub-Family C Proteins; C102029:ABCC6 protein, human