Lack of cyclophilin B in osteogenesis imperfecta with normal collagen folding.
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.
Barnes
Aileen M
AM
National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Carter
Erin M
EM
Cabral
Wayne A
WA
Weis
MaryAnn
M
Chang
Weizhong
W
Makareeva
Elena
E
Leikin
Sergey
S
Rotimi
Charles N
CN
Eyre
David R
DR
Raggio
Cathleen L
CL
Marini
Joan C
JC
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
D018387:Codon, Initiator; C081786:cyclophilin B; D003094:Collagen; D011393:Procollagen-Proline Dioxygenase; C030606:proline, 2-oxoglutarate 3-dioxygenase; D021983:Cyclophilins