Mutations in the COL1A1 and COL1A2 genes associated with osteogenesis imperfecta (OI) types I or III
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Although over 85% of osteogenesis imperfecta (OI) cases are associated with mutations in the procollagen type I genes (COL1A1 or COL1A2), no hot spots for the mutations were associated with particular clinical phenotypes. Eight patients that were studied here, diagnosed with OI by clinical standards, are from the Polish population with no ethnic background indicated. Previously unpublished mutations were found in six out of those eight patients. Genotypes for polymorphisms (Sp1 - rs1800012 and PvuII - rs412777), linked to bone formation and metabolism were determined. Mutations were found in exons 2, 22, 50 and in introns 13 and 51 of the COL1A1 gene. In COL1A2, one mutation was identified in exon 22. Deletion type mutations in COL1A1 that resulted in OI type I had no effect on collagen type I secretion, nor on its intracellular accumulation. Also, a single base substitution in I13 (c.904-9 G>T) was associated with the OI type I. The OI type III was associated with a single base change in I51 of COL1A1, possibly causing an exon skipping. Also, a missense mutation in COL1A2 changing Gly→Cys in the central part of the triple helical domain of the collagen type I molecule caused OI type III. It affected secretion of the heterotrimeric form of procollagen type I. However, no intracellular accumulation of procollagen chains could be detected. Mutation in COL1A2 affected its incorporation into procollagen type I. The results obtained shall help in genetic counseling of OI patients and provide a rational support for making informed, life important decisions by them and their families.
- Blades HZ, Arundel P, Carlino WA, Dalton A, Crook JS, Freeman JV, Bishop NJ (2010) Collagen gene polymorphisms influence risk, and bone mass acquisition during childhood and adolescent growth. Bone 47: 989-994. doi: 10.1016/j.bone.2010.08.014.
- Byers PH, Wallis GA, Willing MC (1991) Osteogenesis imperfecta: translation of mutation to phenotype. J Med Genet 28: 433-442.
- Dalgleish R (1997) The human type I collagen mutation database. Nucleic Acids Res 25: 181-187.
- Dalgleish R (1998) The human collagen mutation database 1998. Nucleic Acids Res 26: 253-255.
- Database. Osteogenesis imperfecta & Ehlers-Danlos syndrome variant databases. Available from: http://www.le.ac.uk/ge/collagen/
- Dehghan M, Pourahmad-Jaktaji R (2015) Sp1 binding site polymorphism of a collagen gene (rs 1800012) in women aged 45 and over and its association with bone density. Turk J Med Sci 45: 644-650.
- Di Lullo GA, Sweeney SM, Körkkö J, Ala-Kokko L, San Antonio JD (2002) Mapping the ligand-binding sites and disease-associated mutations on the most abundant protein in the human, type I collagen. J Biol Chem 277: 4223-4231. doi: 10.1074/jbc.M110709200.
- Forlino A, Cabral WA, Barnes AM, Marini JC (2011) New perspectives on osteogenesis imperfecta. Nat Rev Endocrinol 7: 540-557. doi: 10.1038/nrendo.2011.81.
- Galicka A (2012) Mutations of noncollagen genes in osteogenesis imperfecta-implications of the gene products in collagen biosynthesis and pathogenesis of disease. Postepy Hig Med Dosw 66: 359-371 (in Polish).
- Grant SF, Reid DM, Blake G, Herd R, Fogelman I, Ralston SH (1996) Reduced bone density and osteoporosis associated with a polymorphic Sp1 binding site in the collagen type I α1 gene. Nat Genet 14: 203-205. doi: 10.1038/ng1096-203.
- Katz J, Gong Y, Salmasinia D, Salmasinia D, Hou W, Burkley B, Ferreira P, Casanova O, Langaee TY, Moreb JS (2011) Genetic polymorphisms and other risk factors associated with bisphosphonate induced osteonecrosis of the jaw. Int J Oral Maxillofac Surg 40: 605-611. doi: 10.1016/j.ijom.2011.02.002.
- Kurt-Sirin O, Yilmaz-Aydogan H, Uyar M, Seyhan MF, Isbir T, Can A (2014) Combined effects of collagen type 1 alpha1 (COL1A1) Sp1 polymorphism and osteoporosis risk factors on bone mineral density in Turkish postmenopausal women. Gene 540: 226-231. doi: 10.1016/j.gene.2014.02.028.
- Majka M, Janeczko M, Gozdzik J, Jarocha D, Auguściak-Duma A, Witecka J, Lesiak M, Koryciak-Komarska H, Sieroń AL, Pietrzyk JJ (2013) Cell therapy of patient with type III osteogenesis imperfecta caused by mutation in COL1A2 gene and unstable collagen type I. OJGEN 3: 49-60. doi: 10.4236/ojgen.2013.31006
- Mann V, Hobson EE, Li B, Stewart TL, Grant SF, Robins SP, Aspden RM, Ralston SH (2001) A COL1A1 Sp1 binding site polymorphism predisposes to osteoporotic fracture by affecting bone density and quality. J Clin Invest 107: 899-907. doi: 10.1172/JCI10347.
- Pace JM, Wiese M, Drenguis AS, Kuznetsova N, Leikin S, Schwarze U, Chen D, Mooney SH, Unger S, Byers PH (2008) Defective C-propeptides of the proalpha2(I) chain of type I procollagen impede molecular assembly and result in osteogenesis imperfecta. J Biol Chem 283: 16061-16067. doi: 10.1074/jbc.M801982200.
- Roughley PJ, Rauch F, Glorieux FH (2003) Osteogenesis imperfecta-clinical and molecular diversity. Eur Cell Mater 5: 41-47.
- Sezer S, Simsek N, Celik HT, Erden G, Ozturk G, Duzgun AP, Coskun F, Demircan K (2014) Association of collagen type 1 alpha 1 gene polymorphism with inguinal hernia. Hernia 18: 507-512. doi: 10.1007/s10029-013-1147-y.
- Sillence DO, Rimoin DL (1978) Classification of osteogenesis imperfect. Lancet 1(8072): 1041-1042.
- Sillence DO, Senn A, Danks DM (1979) Genetic heterogeneity in osteogenesis imperfecta. J Med Genet 16: 101-116.
- Stephen J, Shukla A, Dalal A, Girisha KM, Shah H, Gupta N, Kabra M, Dabadghao P, Hasegawa K, Tanaka H, Phadke SR (2014) Mutation spectrum of COL1A1 and COL1A2 genes in Indian patients with osteogenesis imperfecta. Am J Med Genet A 164A: 1482-1489. doi: 10.1002/ajmg.a.36481.
- Suuriniemi M, Kovanen V, Mahonen A, Alen M, Wang Q, Lyytikainen A, Cheng S (2006) COL1A1 Sp1 polymorphism associates with bone density in early puberty. Bone 39: 591-597. doi: 10.1016/j.bone.2006.02.053.
- Tarnowski M, Sieron AL (2008) Osteogenesis imperfecta-etiology, characteristics, current and future treatment. Wiad Lek 61: 166-172 (in Polish).
- van Dijk FS, Cobben JM, Kariminejad A, Maugeri A, Nikkels PG, van Rijn RR, Pals G (2011) Osteogenesis imperfecta: A Review with Clinical Examples. Mol Syndromol 2: 1-20. doi: 10.1159/000332228.
- van Dijk F, Sillence D (2014) Osteogenesis imperfecta: Clinical diagnosis, nomenclature and severity assessment. Am J Med Genet A 164A: 1470-1481. doi: 10.1002/ajmg.a.36545.
- Warman ML, Cormier-Daire V, Hall C, Krakow D, Lachman R, LeMerrer M, Mortier G, Mundlos S, Nishimura G, Rimoin DL, Robertson S, Savarirayan R, Sillence D, Spranger J, Unger S, Zabel B, Superti-Furga A (2011) Nosology and classification of genetic skeletal disorders: 2010 revision. Am J Med Genet A 155A: 943-968. doi: 10.1002/ajmg.a.33909.
- Witecka J, Auguściak-Duma AM, Kruczek A, Szydło A, Lesiak M, Krzak M, Pietrzyk JJ, Mannikko M, Sieroń AL (2008) Two novel COL1A1 mutations in patients with osteogenesis imperfecta (OI) affect the stability of the collagen type I triple-helix. J Appl Genet 49: 283-295. doi: 10.1007/BF03195625.
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