TY - JOUR
T1 - PPIB mutations cause severe osteogenesis imperfecta
AU - van Dijk, Fleur S.
AU - Nesbitt, Isabel M.
AU - Zwikstra, Eline H.
AU - Nikkels, Peter G. J.
AU - Piersma, Sander R.
AU - Fratantoni, Silvina A.
AU - Jimenez, Connie R.
AU - Huizer, Margriet
AU - Morsman, Alice C.
AU - Cobben, Jan M.
AU - van Roij, Mirjam H. H.
AU - Elting, Mariet W.
AU - Verbeke, Jonathan I. M. L.
AU - Wijnaendts, Liliane C. D.
AU - Shaw, Nick J.
AU - Högler, Wolfgang
AU - McKeown, Carole
AU - Sistermans, Erik A.
AU - Dalton, Ann
AU - Meijers-Heijboer, Hanne
AU - Pals, Gerard
AU - Hogler, W.
PY - 2009
Y1 - 2009
N2 - Deficiency of cartilage-associated protein (CRTAP) or prolyl 3-hydroxylase 1(P3H1) has been reported in autosomal-recessive lethal or severe osteogenesis imperfecta (OI). CRTAP, P3H1, and cyclophilin B (CyPB) form an intracellular collagen-modifying complex that 3-hydroxylates proline at position 986 (P986) in the alpha1 chains of collagen type I. This 3-prolyl hydroxylation is decreased in patients with CRTAP and P3H1 deficiency. It was suspected that mutations in the PPIB gene encoding CyPB would also cause OI with decreased collagen 3-prolyl hydroxylation. To our knowledge we present the first two families with recessive OI caused by PPIB gene mutations. The clinical phenotype is compatible with OI Sillence type II-B/III as seen with COL1A1/2, CRTAP, and LEPRE1 mutations. The percentage of 3-hydroxylated P986 residues in patients with PPIB mutations is decreased in comparison to normal, but it is higher than in patients with CRTAP and LEPRE1 mutations. This result and the fact that CyPB is demonstrable independent of CRTAP and P3H1, along with reported decreased 3-prolyl hydroxylation due to deficiency of CRTAP lacking the catalytic hydroxylation domain and the known function of CyPB as a cis-trans isomerase, suggest that recessive OI is caused by a dysfunctional P3H1/CRTAP/CyPB complex rather than by the lack of 3-prolyl hydroxylation of a single proline residue in the alpha1 chains of collagen type I
AB - Deficiency of cartilage-associated protein (CRTAP) or prolyl 3-hydroxylase 1(P3H1) has been reported in autosomal-recessive lethal or severe osteogenesis imperfecta (OI). CRTAP, P3H1, and cyclophilin B (CyPB) form an intracellular collagen-modifying complex that 3-hydroxylates proline at position 986 (P986) in the alpha1 chains of collagen type I. This 3-prolyl hydroxylation is decreased in patients with CRTAP and P3H1 deficiency. It was suspected that mutations in the PPIB gene encoding CyPB would also cause OI with decreased collagen 3-prolyl hydroxylation. To our knowledge we present the first two families with recessive OI caused by PPIB gene mutations. The clinical phenotype is compatible with OI Sillence type II-B/III as seen with COL1A1/2, CRTAP, and LEPRE1 mutations. The percentage of 3-hydroxylated P986 residues in patients with PPIB mutations is decreased in comparison to normal, but it is higher than in patients with CRTAP and LEPRE1 mutations. This result and the fact that CyPB is demonstrable independent of CRTAP and P3H1, along with reported decreased 3-prolyl hydroxylation due to deficiency of CRTAP lacking the catalytic hydroxylation domain and the known function of CyPB as a cis-trans isomerase, suggest that recessive OI is caused by a dysfunctional P3H1/CRTAP/CyPB complex rather than by the lack of 3-prolyl hydroxylation of a single proline residue in the alpha1 chains of collagen type I
U2 - https://doi.org/10.1016/j.ajhg.2009.09.001
DO - https://doi.org/10.1016/j.ajhg.2009.09.001
M3 - Article
C2 - 19781681
SN - 0002-9297
VL - 85
SP - 521
EP - 527
JO - American journal of human genetics
JF - American journal of human genetics
IS - 4
ER -