title: Lack of cyclophilin B in osteogenesis imperfecta with normal collagen folding.
abstract: Osteogenesis imperfecta is a heritable disorder that causes bone fragility. Mutations in type I collagen result in autosomal dominant osteogenesis imperfecta, whereas mutations in either of two components of the collagen prolyl 3-hydroxylation complex (cartilage-associated protein [CRTAP] and prolyl 3-hydroxylase 1 [P3H1]) cause autosomal recessive osteogenesis imperfecta with rhizomelia (shortening of proximal segments of upper and lower limbs) and delayed collagen folding. We identified two siblings who had recessive osteogenesis imperfecta without rhizomelia. They had a homozygous start-codon mutation in the peptidyl-prolyl isomerase B gene (PPIB), which results in a lack of cyclophilin B (CyPB), the third component of the complex. The proband's collagen had normal collagen folding and normal prolyl 3-hydroxylation, suggesting that CyPB is not the exclusive peptidyl-prolyl cis-trans isomerase that catalyzes the rate-limiting step in collagen folding, as is currently thought.
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: Erin M
authors.initials: EM
authors.lastname: Carter
authors.forename: Wayne A
authors.initials: WA
authors.lastname: Cabral
authors.forename: MaryAnn
authors.initials: M
authors.lastname: Weis
authors.forename: Weizhong
authors.initials: W
authors.lastname: Chang
authors.forename: Elena
authors.initials: E
authors.lastname: Makareeva
authors.forename: Sergey
authors.initials: S
authors.lastname: Leikin
authors.forename: Charles N
authors.initials: CN
authors.lastname: Rotimi
authors.forename: David R
authors.initials: DR
authors.lastname: Eyre
authors.forename: Cathleen L
authors.initials: CL
authors.lastname: Raggio
authors.forename: Joan C
authors.initials: JC
authors.lastname: Marini
mesh_terms: D002648:Child; D002675:Child, Preschool; D018387:Codon, Initiator / Q000235:genetics*; D003094:Collagen / Q000378:metabolism; D021983:Cyclophilins / Q000172:deficiency* / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive; D006801:Humans; D008297:Male; D009154:Mutation; D010013:Osteogenesis Imperfecta / Q000235:genetics* / Q000378:metabolism; D010375:Pedigree; D010641:Phenotype; D011393:Procollagen-Proline Dioxygenase / Q000378:metabolism; D017510:Protein Folding
chemical_list: D018387:Codon, Initiator; C081786:cyclophilin B; D003094:Collagen; D011393:Procollagen-Proline Dioxygenase; C030606:proline, 2-oxoglutarate 3-dioxygenase; D021983:Cyclophilins