title: Mutations in a gene encoding an ABC transporter cause pseudoxanthoma elasticum.
abstract: Pseudoxanthoma elasticum (PXE) is a heritable disorder characterized by calcification of elastic fibres in skin, arteries and retina that results in dermal lesions with associated laxity and loss of elasticity, arterial insufficiency and retinal haemorrhages leading to macular degeneration. PXE is usually found as a sporadic disorder, but examples of both autosomal recessive and autosomal dominant forms of PXE have been observed. Partial manifestations of the PXE phenotype have also been described in presumed carriers in PXE families. Linkage of both dominant and recessive forms of PXE to a 5-cM domain on chromosome 16p13.1 has been reported (refs 8,9). We have refined this locus to an 820-kb region containing 6 candidate genes. Here we report the exclusion of five of these genes and the identification of the first mutations responsible for the development of PXE in a gene encoding a protein associated with multidrug resistance (ABCC6).
authors.affiliation: Laboratory of Matrix Pathobiology, Pacific Biomedical Research Center, University of Hawai'i, Honolulu, Hawai'i, USA.
authors.forename: O
authors.initials: O
authors.lastname: Le Saux
authors.forename: Z
authors.initials: Z
authors.lastname: Urban
authors.forename: C
authors.initials: C
authors.lastname: Tschuch
authors.forename: K
authors.initials: K
authors.lastname: Csiszar
authors.forename: B
authors.initials: B
authors.lastname: Bacchelli
authors.forename: D
authors.initials: D
authors.lastname: Quaglino
authors.forename: I
authors.initials: I
authors.lastname: Pasquali-Ronchetti
authors.forename: F M
authors.initials: FM
authors.lastname: Pope
authors.forename: A
authors.initials: A
authors.lastname: Richards
authors.forename: S
authors.initials: S
authors.lastname: Terry
authors.forename: L
authors.initials: L
authors.lastname: Bercovitch
authors.forename: A
authors.initials: A
authors.lastname: de Paepe
authors.forename: C D
authors.initials: CD
authors.lastname: Boyd
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000737:chemistry / Q000235:genetics*; D000595:Amino Acid Sequence; D001483:Base Sequence; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics; D015331:Cohort Studies; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D008040:Genetic Linkage / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011487:Protein Conformation; D011561:Pseudoxanthoma Elasticum / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D018528:ATP-Binding Cassette Transporters; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D012333:RNA, Messenger