title: Pseudoxanthoma elasticum is a recessive disease characterized by compound heterozygosity.
abstract: Pseudoxanthoma elasticum (PXE) is caused by mutations in the ABCC6 gene. Historically, PXE has been suggested to be inherited either in an autosomal dominant or autosomal recessive manner. To determine the exact mode of inheritance of PXE and to address the question of phenotypic expression in mutation carriers, we identified seven pedigrees with affected individuals in two different generations and sequenced the entire coding region of ABCC6 in affected individuals, presumed carriers with a limited phenotype and unaffected family members. Two allelic mutations were identified in each individual with unambiguous diagnosis of PXE, as well as in those with only minimal clinical signs suggestive of PXE but with positive skin biopsy. Missense mutations were frequently detected in the latter cases. In conclusion, PXE is inherited in an autosomal recessive manner and presence of disease in two generations is due to pseudodominance.
authors.affiliation: Department of Dermatology and Cutaneous Biology, Jefferson Medical College, Philadelphia, Pennsylvania 19107, USA. franziska.ringpfeil@jefferson.edu
authors.forename: Franziska
authors.initials: F
authors.lastname: Ringpfeil
authors.forename: Kelly
authors.initials: K
authors.lastname: McGuigan
authors.forename: Lauren
authors.initials: L
authors.lastname: Fuchsel
authors.forename: Heidi
authors.initials: H
authors.lastname: Kozic
authors.forename: Margarita
authors.initials: M
authors.lastname: Larralde
authors.forename: Mark
authors.initials: M
authors.lastname: Lebwohl
authors.forename: Jouni
authors.initials: J
authors.lastname: Uitto
mesh_terms: D004252:DNA Mutational Analysis; D005808:Genes, Recessive; D006579:Heterozygote; D006801:Humans; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D011561:Pseudoxanthoma Elasticum / Q000235:genetics*
chemical_list: D027425:ATP-Binding Cassette, Sub-Family C Proteins; C102029:ABCC6 protein, human