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CRTAP and LEPRE1 mutations in recessive osteogenesis imperfecta.
Hum Mutat. 2008 Dec; 29(12):1435-42.HM

Abstract

Autosomal dominant osteogenesis imperfecta (OI) is caused by mutations in the genes (COL1A1 or COL1A2) encoding the chains of type I collagen. Recently, dysregulation of hydroxylation of a single proline residue at position 986 of both the triple-helical domains of type I collagen alpha1(I) and type II collagen alpha1(II) chains has been implicated in the pathogenesis of recessive forms of OI. Two proteins, cartilage-associated protein (CRTAP) and prolyl-3-hydroxylase-1 (P3H1, encoded by the LEPRE1 gene) form a complex that performs the hydroxylation and brings the prolyl cis-trans isomerase cyclophilin-B (CYPB) to the unfolded collagen. In our screen of 78 subjects diagnosed with OI type II or III, we identified three probands with mutations in CRTAP and 16 with mutations in LEPRE1. The latter group includes a mutation in patients from the Irish Traveller population, a genetically isolated community with increased incidence of OI. The clinical features resulting from CRTAP or LEPRE1 loss of function mutations were difficult to distinguish at birth. Infants in both groups had multiple fractures, decreased bone modeling (affecting especially the femurs), and extremely low bone mineral density. Interestingly, "popcorn" epiphyses may reflect underlying cartilaginous and bone dysplasia in this form of OI. These results expand the range of CRTAP/LEPRE1 mutations that result in recessive OI and emphasize the importance of distinguishing recurrence of severe OI of recessive inheritance from those that result from parental germline mosaicism for COL1A1 or COL1A2 mutations.

Authors+Show Affiliations

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18566967

Citation

Baldridge, Dustin, et al. "CRTAP and LEPRE1 Mutations in Recessive Osteogenesis Imperfecta." Human Mutation, vol. 29, no. 12, 2008, pp. 1435-42.
Baldridge D, Schwarze U, Morello R, et al. CRTAP and LEPRE1 mutations in recessive osteogenesis imperfecta. Hum Mutat. 2008;29(12):1435-42.
Baldridge, D., Schwarze, U., Morello, R., Lennington, J., Bertin, T. K., Pace, J. M., Pepin, M. G., Weis, M., Eyre, D. R., Walsh, J., Lambert, D., Green, A., Robinson, H., Michelson, M., Houge, G., Lindman, C., Martin, J., Ward, J., Lemyre, E., ... Lee, B. (2008). CRTAP and LEPRE1 mutations in recessive osteogenesis imperfecta. Human Mutation, 29(12), 1435-42. https://doi.org/10.1002/humu.20799
Baldridge D, et al. CRTAP and LEPRE1 Mutations in Recessive Osteogenesis Imperfecta. Hum Mutat. 2008;29(12):1435-42. PubMed PMID: 18566967.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - CRTAP and LEPRE1 mutations in recessive osteogenesis imperfecta. AU - Baldridge,Dustin, AU - Schwarze,Ulrike, AU - Morello,Roy, AU - Lennington,Jennifer, AU - Bertin,Terry K, AU - Pace,James M, AU - Pepin,Melanie G, AU - Weis,Maryann, AU - Eyre,David R, AU - Walsh,Jennifer, AU - Lambert,Deborah, AU - Green,Andrew, AU - Robinson,Haynes, AU - Michelson,Melonie, AU - Houge,Gunnar, AU - Lindman,Carl, AU - Martin,Judith, AU - Ward,Jewell, AU - Lemyre,Emmanuelle, AU - Mitchell,John J, AU - Krakow,Deborah, AU - Rimoin,David L, AU - Cohn,Daniel H, AU - Byers,Peter H, AU - Lee,Brendan, PY - 2008/6/21/pubmed PY - 2009/1/9/medline PY - 2008/6/21/entrez SP - 1435 EP - 42 JF - Human mutation JO - Hum Mutat VL - 29 IS - 12 N2 - Autosomal dominant osteogenesis imperfecta (OI) is caused by mutations in the genes (COL1A1 or COL1A2) encoding the chains of type I collagen. Recently, dysregulation of hydroxylation of a single proline residue at position 986 of both the triple-helical domains of type I collagen alpha1(I) and type II collagen alpha1(II) chains has been implicated in the pathogenesis of recessive forms of OI. Two proteins, cartilage-associated protein (CRTAP) and prolyl-3-hydroxylase-1 (P3H1, encoded by the LEPRE1 gene) form a complex that performs the hydroxylation and brings the prolyl cis-trans isomerase cyclophilin-B (CYPB) to the unfolded collagen. In our screen of 78 subjects diagnosed with OI type II or III, we identified three probands with mutations in CRTAP and 16 with mutations in LEPRE1. The latter group includes a mutation in patients from the Irish Traveller population, a genetically isolated community with increased incidence of OI. The clinical features resulting from CRTAP or LEPRE1 loss of function mutations were difficult to distinguish at birth. Infants in both groups had multiple fractures, decreased bone modeling (affecting especially the femurs), and extremely low bone mineral density. Interestingly, "popcorn" epiphyses may reflect underlying cartilaginous and bone dysplasia in this form of OI. These results expand the range of CRTAP/LEPRE1 mutations that result in recessive OI and emphasize the importance of distinguishing recurrence of severe OI of recessive inheritance from those that result from parental germline mosaicism for COL1A1 or COL1A2 mutations. SN - 1098-1004 UR - https://www.unboundmedicine.com/medline/citation/18566967/CRTAP_and_LEPRE1_mutations_in_recessive_osteogenesis_imperfecta_ L2 - https://doi.org/10.1002/humu.20799 DB - PRIME DP - Unbound Medicine ER -