Deficiency of cartilage-associated protein in recessive lethal osteogenesis imperfecta.
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.
Barnes
Aileen M
AM
National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Chang
Weizhong
W
Morello
Roy
R
Cabral
Wayne A
WA
Weis
MaryAnn
M
Eyre
David R
DR
Leikin
Sergey
S
Makareeva
Elena
E
Kuznetsova
Natalia
N
Uveges
Thomas E
TE
Ashok
Aarthi
A
Flor
Armando W
AW
Mulvihill
John J
JJ
Wilson
Patrick L
PL
Sundaram
Usha T
UT
Lee
Brendan
B
Marini
Joan C
JC
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
C108053:CRTAP protein, human; D024042:Collagen Type I; D016326:Extracellular Matrix Proteins; D018832:Molecular Chaperones