title: Deficiency of cartilage-associated protein in recessive lethal osteogenesis imperfecta.
abstract: Classic osteogenesis imperfecta, an autosomal dominant disorder associated with osteoporosis and bone fragility, is caused by mutations in the genes for type I collagen. A recessive form of the disorder has long been suspected. Since the loss of cartilage-associated protein (CRTAP), which is required for post-translational prolyl 3-hydroxylation of collagen, causes severe osteoporosis in mice, we investigated whether CRTAP deficiency is associated with recessive osteogenesis imperfecta. Three of 10 children with lethal or severe osteogenesis imperfecta, who did not have a primary collagen defect yet had excess post-translational modification of collagen, were found to have a recessive condition resulting in CRTAP deficiency, suggesting that prolyl 3-hydroxylation of type I collagen is important for bone formation.
authors.affiliation: National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Aileen M
authors.initials: AM
authors.lastname: Barnes
authors.forename: Weizhong
authors.initials: W
authors.lastname: Chang
authors.forename: Roy
authors.initials: R
authors.lastname: Morello
authors.forename: Wayne A
authors.initials: WA
authors.lastname: Cabral
authors.forename: MaryAnn
authors.initials: M
authors.lastname: Weis
authors.forename: David R
authors.initials: DR
authors.lastname: Eyre
authors.forename: Sergey
authors.initials: S
authors.lastname: Leikin
authors.forename: Elena
authors.initials: E
authors.lastname: Makareeva
authors.forename: Natalia
authors.initials: N
authors.lastname: Kuznetsova
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Uveges
authors.forename: Aarthi
authors.initials: A
authors.lastname: Ashok
authors.forename: Armando W
authors.initials: AW
authors.lastname: Flor
authors.forename: John J
authors.initials: JJ
authors.lastname: Mulvihill
authors.forename: Patrick L
authors.initials: PL
authors.lastname: Wilson
authors.forename: Usha T
authors.initials: UT
authors.lastname: Sundaram
authors.forename: Brendan
authors.initials: B
authors.lastname: Lee
authors.forename: Joan C
authors.initials: JC
authors.lastname: Marini
mesh_terms: D024042:Collagen Type I / Q000737:chemistry; D004252:DNA Mutational Analysis; D016326:Extracellular Matrix Proteins / Q000032:analysis / Q000172:deficiency* / Q000235:genetics*; D005260:Female; D005347:Fibroblasts / Q000737:chemistry; D005808:Genes, Recessive; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D018832:Molecular Chaperones; D009154:Mutation; D010013:Osteogenesis Imperfecta / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology*; D011859:Radiography; D016216:Ultrasonography, Prenatal
chemical_list: C108053:CRTAP protein, human; D024042:Collagen Type I; D016326:Extracellular Matrix Proteins; D018832:Molecular Chaperones