title: Mutations of the gene encoding the transmembrane transporter protein ABC-C6 cause pseudoxanthoma elasticum.
abstract: We recently published the precise chromosomal localization on chromosome 16p13.1 of the genetic defect underlying pseudoxanthoma elasticum (PXE), an inherited disorder characterized by progressive calcification of elastic fibers in skin, eye, and the cardiovascular system. Here we report the identification of mutations in the gene encoding the transmembrane transporter protein, ABC-C6 (also known as MRP-6), one of the four genes located in the region of linkage, as cause of the disease. Sequence analysis in four independent consanguineous families from Switzerland, Mexico, and South Africa and in one non-consanguineous family from the United States demonstrated several different mis-sense mutations to cosegregate with the disease phenotype. These findings are consistent with the conclusion that PXE is a recessive disorder that displays allelic heterogeneity, which may explain the considerable phenotypic variance characteristic of the disorder.
authors.affiliation: Department of Cardiology, Children's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: B
authors.initials: B
authors.lastname: Struk
authors.forename: L
authors.initials: L
authors.lastname: Cai
authors.forename: S
authors.initials: S
authors.lastname: Zäch
authors.forename: W
authors.initials: W
authors.lastname: Ji
authors.forename: J
authors.initials: J
authors.lastname: Chung
authors.forename: A
authors.initials: A
authors.lastname: Lumsden
authors.forename: M
authors.initials: M
authors.lastname: Stumm
authors.forename: M
authors.initials: M
authors.lastname: Huber
authors.forename: L
authors.initials: L
authors.lastname: Schaen
authors.forename: C A
authors.initials: CA
authors.lastname: Kim
authors.forename: L A
authors.initials: LA
authors.lastname: Goldsmith
authors.forename: D
authors.initials: D
authors.lastname: Viljoen
authors.forename: L E
authors.initials: LE
authors.lastname: Figuera
authors.forename: W
authors.initials: W
authors.lastname: Fuchs
authors.forename: F
authors.initials: F
authors.lastname: Munier
authors.forename: R
authors.initials: R
authors.lastname: Ramesar
authors.forename: D
authors.initials: D
authors.lastname: Hohl
authors.forename: R
authors.initials: R
authors.lastname: Richards
authors.forename: K H
authors.initials: KH
authors.lastname: Neldner
authors.forename: K
authors.initials: K
authors.lastname: Lindpaintner
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D003241:Consanguinity; D005260:Female; D006239:Haplotypes / Q000235:genetics; D006720:Homozygote; D006801:Humans; D008297:Male; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009154:Mutation; D010375:Pedigree; D017354:Point Mutation; D012150:Polymorphism, Restriction Fragment Length; D011561:Pseudoxanthoma Elasticum / Q000235:genetics*
chemical_list: D018528:ATP-Binding Cassette Transporters; D027425:ATP-Binding Cassette, Sub-Family C Proteins