OJGen  Vol.3 No.1 , March 2013
Cell therapy of a patient with type III osteogenesis imperfecta caused by mutation in COL1A2 gene and unstable collagen type I
ABSTRACT
The allogenic bone marrow derived mesenchymal stem cells transplantation was given to the newborn girl diagnosed with osteogenesis imperfecta type III, with multiple bone fractures, extreme shortness and limbs deformities. The treatment was performed at the age of 4 and 6 weeks. The clinical diagnosis was supported by biochemical analysis of collagen type I recovered from culture medium of cultivated patient’s skin fibroblast, which revealed its triple helix instability at temperature about 2?C lower than normal. Sequencing of both genes encoding procollagen type I revealed heterozygous substitution G23569Ain COL1A2 gene causing change of glycine at position 517 to aspartate. The donor of mesenchymal stem cells was the girl’s father. She received two intravenous infusions of suspended cultured mesenchymal cells in 16 days apart without any side effects. An analysis of procollagen type I secreted to the culture medium by bone marrow-derived mesenchymal stem cells obtained from the patient, 3 months following transplantation revealed its normal triple helix stability. During the subsequent two years of follow up two new bone fractures were noted. Currently a two-year-old girl’s presents extreme growth and weight deficiency. The motoric development is also retarded, but the patient constantly improves and makes progresses.

Cite this paper
Majka, M. , Janeczko, M. , Goździk, J. , Jarocha, D. , Auguściak-Duma, A. , Witecka, J. , Lesiak, M. , Koryciak-Komarska, H. , Sieroń, A. and Pietrzyk, J. (2013) Cell therapy of a patient with type III osteogenesis imperfecta caused by mutation in COL1A2 gene and unstable collagen type I. Open Journal of Genetics, 3, 49-60. doi: 10.4236/ojgen.2013.31006.
References
[1]   Rauch, F. and Glorieux, F.H. (2004) Osteogenesis imperfecta. Lancet, 363, 1377-1385. doi:10.1016/S0140-6736(04)16051-0

[2]   Plotkin, H. (2004) Syndromes with congenital brittle bones. BMC Pediatrics, 4, 16. doi:10.1186/1471-2431-4-16

[3]   Glorieux, F.H. (2008) Osteogenesis imperfecta. Best Practice & Research Clinical Rheumatology, 22, 85-100. doi:10.1016/j.berh.2007.12.012

[4]   Van Dijk, F.S., Pals, G., Van Rijn, R.R., Nikkels, P.G. and Cobben, J.M. (2010) Classification of osteogenesis imperfecta revisited. European Journal of Medical Genetics, 53, 1-5. doi:10.1016/j.ejmg.2009.10.007

[5]   Hackley, L. and Merritt, L. (2008) Osteogenesis imperfecta in the neonate. Advances in Neonatal Care, 8, 21-30. doi:10.1097/01.ANC.0000311013.71510.41

[6]   Morgan, J.A. and Marcus, P.S. (2010) Prenatal diagnosis and management of intrauterine fracture. Obstetrical & Gynecological Survey, 65, 249-259. doi:10.1097/OGX.0b013e3181dbc50b

[7]   Tedeschi, E., Antoniazzi, F., Venturi, G., Zamboni, G. and Tatò, L. (2006) Osteogenesis imperfecta and its molecular diagnosis by determination of mutations of type I collagen genes. Pediatric Endocrinology Reviews, 4, 40-46.

[8]   Burnei, G., Vlad, C., Georgescu, I. and Gavriliu, T.S. (2008) Osteogenesis imperfecta: Diagnosis and treatment. Journal of the American Academy of Orthopaedic Surgeons, 16, 356-366.

[9]   Basel, D. and Steiner, R.D. (2009) Osteogenesis imperfecta: Recent findings shed new light on this once well-understood condition. Genetics in Medicine, 11, 375-385. doi:10.1097/GIM.0b013e3181a1ff7b

[10]   Marini, J.C., Cabral, W.A., Barnes, A.M., Chang and W. (2007) Components of the collagen prolyl 3-hydroxy-lation complex are crucial for normal bone development. Cell Cycle, 6, 1675-1681. doi:10.4161/cc.6.14.4474

[11]   Tarnowski, M. and Sieroń, A.L. (2008) Osteogenesis imperfecta-etiology, characteristics, current and future treatment. Wiadomosci Lekarskie, 61, 166-172.

[12]   Dent, C.E. and Davies, I.J. (1980) Calcium metabolism in bone disease: Effects of treatment with microcrystalline calcium hydroxyapatite compound and dihydrotachysterol. Journal of the Royal Society of Medicine, 73, 780-785.

[13]   Bachrach, L.K. and Ward, L.M. (2009) Clinical review 1: Bisphosphonate use in childhood osteoporosis. The Journal of Clinical Endocrinology & Metabolism, 94, 400-409. doi:10.1210/jc.2008-1531

[14]   Russell, R.G. (2007) Bisphosphonates: Mode of action and pharmacology. Pediatrics, 119, 150-162. doi:10.1542/peds.2006-2023H

[15]   Benhamou, C.L. (2007) Effects of osteoporosis medications on bone quality. Joint Bone Spine, 74, 39-47. doi:10.1016/j.jbspin.2006.06.004

[16]   Rauch, F. and Glorieux, F.H. (2005) Bisphosphonate treatment in osteogenesis imperfecta: Which drug, for whom, for how long? Annals of Medicine, 37, 295-302. doi:10.1080/07853890510007386

[17]   Horwitz, E.M., Prockop, D.J., Fitzpatrick, L.A., et al., (1999) Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta. Nature Medicine, 5, 309-313. doi:10.1038/6529

[18]   Horwitz, E.M., Prockop, D.J., Gordon, P.L., et al., (2001) Clinical responses to bone marrow transplantation in children with severe osteogenesis imperfecta. Blood, 97, 1227-1231. doi:10.1182/blood.V97.5.1227

[19]   Pochampally, R.R., Horwitz, E.M., DiGirolamo, C.M., Stokes, D.S. and Prockop, D.J. (2005) Correction of a mineralization defect by overexpression of a wild-type cDNA for COL1A1 in marrow stromal cells (MSCs) from a patient with osteogenesis imperfecta: A strategy for rescuing mutations that produce dominant-negative protein defects. Gene Therapy, 12, 1119-1125. doi:10.1038/sj.gt.3302514

[20]   Niyibizi, C. and Li, F. (2009) Potential implications of cell therapy for osteogenesis imperfecta. International Journal of Clinical Rheumatology, 4, 57-66.

[21]   Sillence, D.O., Senn, A. and Danks, D.M. (1979) Genetic heterogeneity in osteogenesis imperfecta. Journal of Medical Genetics, 16, 101-116. doi:10.1136/jmg.16.2.101

[22]   Witecka, J., Augu?ciak-Duma, A.M., Kruczek, A., et al., (2008) Two novel COL1A1 mutations in patients with osteogenesis imperfecta (OI) affect the stability of the collagen type I triple-helix. Journal of Applied Genetics, 49, 283-295. doi:10.1007/BF03195625

[23]   Fertala, A., Sieron, A.L., Ganguly, A., et al., (1994) Synthesis of recombinant human procollagen II in a stably transfected tumor cell line (HT-1080). Biochemical Journal, 298, 31-37.

[24]   Arnold. W.V., Fertala, A., Sieron, A.L., et al., (1998) Recombinant procollagen II: Deletion of D period segments identifies sequences that are required for helix stabilization and generates a temperature-sensitive N-proteinase cleavage site. The Journal of Biological Chemistry, 273, 31822-31828. doi:10.1074/jbc.273.48.31822

[25]   Stanford, C.M., Jacobson, P.A., Eanes, E.D., Lembke, L.A. and Midura, R.J. (1995) Rapidly forming apatitic mineral in an osteoblastic cell line (UMR 106-01 BSP). The Journal of Biological Chemistry, 270, 9420-9428. doi:10.1074/jbc.270.16.9420

[26]   Gregory, C.A., Gunn, W.G., Peister, A. and Prockop, D.J. (2004) An Alizarin red-based assay of mineralization by adherent cells in culture: comparison with cetylpyridinium chloride extraction. Analytical Biochemistry, 329, 77-84. doi:10.1016/j.ab.2004.02.002

[27]   Marini, J.C., Letocha, A.D. and Chernoff, E.J. (2005) Osteogenesis imperfecta. In: Cassidy, S.B and Allanson, J.E., Eds., Management of genetic syndromes. Published Online: 14 JAN 2005. http://onlinelibrary.wiley.com/doi/10.1002/0471695998.mgs034/abstract

[28]   Esposito, P. and Plotkin, H. (2008) Surgical treatment of osteogenesis imperfecta: Current concepts. Current Opinion in Pediatrics, 20, 52-57. doi:10.1097/MOP.0b013e3282f35f03

[29]   Marini, J. (2010) Osteogenesis imperfecta. In: Diseases of bone and calcium metabolism. South Dartmouth in US: Mdtext.com.inc. http://www.endotext.org/parathyroid/parathyroid17/parathyroidframe17.htm

[30]   Chen, H. (2006) Osteogenesis imperfecta. In: Chen, H., Ed., Atlas of genetic diagnosis and counselling, Humana Press Inc., New Jersey, 762-772.

 
 
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