title: Molecular genetics of pseudoxanthoma elasticum.
abstract: Pseudoxanthoma elasticum (PXE), a systemic heritable connective tissue disorder, is characterized by progressive calcification of elastic structures in the skin, the eyes and the cardiovascular system, with considerable intra- and interfamilial phenotypic variability. Recently, underlying genetic defects have been identified in the ABCC6 gene, which resides on the chromosomal locus 16p13.1 and encodes the MRP6 protein, a member of the ATP-binding cassette (ABC) family of proteins. The affected individuals are homozygous or compound heterozygous for a spectrum of genetic lesions, including nonsense and missense mutations, or deletions and splice-site alterations, confirming the autosomal recessive nature of this condition. Analysis of the deduced primary sequence suggests that MRP6 is a transmembrane transporter, but its function has not been delineated yet. Surprisingly, however, MRP6 is expressed primarily, if not exclusively, in the liver and the kidneys, suggesting that PXE may be a primary metabolic disorder with secondary involvement of elastic fibers. Identification of mutations in the ABCC6 gene in PXE provides a means for prenatal and presymptomatic testing in families at risk for recurrence. DNA-based analyses will also identify heterozygous carriers who may be at risk for development of limited manifestations of the disease as a result of compounding genetic factors and/or environmental modifiers.
authors.affiliation: Department of Dermatology and Cutaneous Biology, Jefferson Medical College, Thomas Jefferson University, 233 S. 10th Street, Philadelphia, PA 19107, USA.
authors.forename: F
authors.initials: F
authors.lastname: Ringpfeil
authors.forename: L
authors.initials: L
authors.lastname: Pulkkinen
authors.forename: J
authors.initials: J
authors.lastname: Uitto
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000502:physiology; D004252:DNA Mutational Analysis; D005820:Genetic Testing; D014644:Genetic Variation; D006801:Humans; D008967:Molecular Biology; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009154:Mutation / Q000502:physiology; D011561:Pseudoxanthoma Elasticum / Q000235:genetics*; D013329:Structure-Activity Relationship
chemical_list: D018528:ATP-Binding Cassette Transporters; D027425:ATP-Binding Cassette, Sub-Family C Proteins