Russian Journal of Genetics

, Volume 48, Issue 3, pp 321–328

Studies of type I collagen (COL1A1) α1 chain in patients with osteogenesis imperfecta

  • D. D. Nadyrshina
  • R. I. Khusainova
  • E. K. Khusnutdinova
Human Genetics


Nucleotide sequences of exon 51, adjacent intron areas, and regulatory region of the α1 chain of type I collagen (COL1A1) gene were analyzed in 41 patients with osteogenesis imperfecta (OI) from 33 families and their 68 relatives residing at Bashkortostan Republic (BR). Six mutations (four nonsense mutations c.967G>T (p.Gly323X), c.1081C>T (p.Arg361X), c.1243C>T (p.Arg415X), and c.2869C>T (p.Gln957X)) in patients of the Russian origin and two frameshift mutations (c.579delT (p.Gly194ValfsX71), and c.2444delG (p.Gly815AlafsX293)) in patients with OI of Tatar ethnicity as well as 14 single nucleotide polymorphisms in the COL1A1 gene were revealed. Mutations c.967G>T (p.Gly323X) and three alterations in the nucleotide sequence c.544-24C>T, c.643-36delT, and c.957 + 10insA were described for the first time.


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  1. 1.
    Liu, W., Gu, F., Ji, J., et al., A Novel COL1A1 Nonsense Mutation Causing Osteogenesis Imperfecta in a Chinese Family, Mol. Vision, 2007, vol. 13, pp. 360–65.Google Scholar
  2. 2.
    Kataoka, K., Ogura, E., Hasegawa, K., et al., Mutations in Type I Collagen Genes in Japanese Osteogenesis Imperfecta Patients, Pediatr. Int., vol. 49, pp. 564–569.Google Scholar
  3. 3.
    Bodian, D.L., Chan, T-F., Poon, A., et al., Mutation and Polymorphism Spectrum in OI Type II: Implication for Genotype-Phenotype Relatioships, Hum. Med. Genet., 2009, vol. 18, pp. 463–471.CrossRefGoogle Scholar
  4. 4.
    Swinnen, F.K., De Leenheer, E.M., Coucke, P.J., et al., Audiometric, Surgical, and Genetic Findings in 15 Ears of Patients with Osteogenesis Imperfect, Laryngoscope, 2009, vol. 119, no. 6, pp. 1171–1179.PubMedCrossRefGoogle Scholar
  5. 5.
    Benusien, E. and Kucinskas, V., COL1A1 Mutation Analysis in Lithuanian Patients with Osteogenesis Imperfect, J. Appl. Genet., 2003, vol. 44, no. 1, pp. 95–102.Google Scholar
  6. 6.
    Venturi, G., Tedeschi, E., Mottes, M., et al., Osteogenesis Imperfecta: Clinical, Biochemical and Molecular Findings, Clin. Genet., 2006, vol. 70, no. 2, pp. 131–139.PubMedCrossRefGoogle Scholar
  7. 7.
    Baldridge, D., Schwarze, U., Morello, R., et al., CRTAP and LEPRE1 Mutations in Recessive Osteogenesis Imperfecta, Hum. Mutat., 2008, pp. 1435–1442.Google Scholar
  8. 8.
    Van Dijk, F.S., Nesbitt, I.M., Zwikstra, E.H., et al., PPIB Mutations Cause Severe Osteogenesis Imperfecta, Am. J. Hum. Genet., 2009, vol. 85, pp. 521–527.PubMedCrossRefGoogle Scholar
  9. 9.
    Alanay, Y., Avaygan, H., Camacho, N., et al., Mutations in the Gene Encoding the RER Protein FKBP65 Cause Autosomal-Recessive Osteogenesis Imperfecta, Am. J. Hum. Genet., 2010, vol. 86, pp. 551–559.PubMedCrossRefGoogle Scholar
  10. 10.
    Barnes, A.M., Chang, W., Morello, R., et al., Deficiency of Cartilage-Associated Protein in Recessive Lethal Osteogenesis Imperfecta, N. Engl. J. Med., 2006, vol. 355, pp. 2757–2764.PubMedCrossRefGoogle Scholar
  11. 11.
    Barnes, A.M., Carter, E.M., Cabral, W.A., et al., Lack of Cyclophilin B in Osteogenesis Imperfecta with Normal Collagen Folding, N. Engl. J. Med., 2010, vol. 362, pp. 521–528.PubMedCrossRefGoogle Scholar
  12. 12.
    Christiansen, H.E., Schwarze, U., Pyott, S.M., et al., Homozygosity for a Missense Mutation in SERPINH1, Which Encodes the Collagen Chaperone Protein HSP47, Results in Severe Recessive Osteogenesis Imperfecta, Am. J. Hum. Genet., 2010, vol. 86, pp. 389–398.PubMedCrossRefGoogle Scholar
  13. 13.
    Lapunzina, P., Aglan, M., Temtamy, S., et al., Identication of a Frameshift Mutation in Osterix in a Patient with Recessive Osteogenesis Imperfecta, Am. J. Hum. Genet., 2010, vol. 87, pp. 110–114.PubMedCrossRefGoogle Scholar
  14. 14.
    Becker, J., Semler, O., Gilissen, C., et al., Exome Sequencing Identifies Truncating Mutations in Human SERPINF1 in Autosomal-Recessive Osteogenesis Imperfecta, Am. J. Hum. Genet., 2011, vol. 11, no. 3, pp. 362–371.CrossRefGoogle Scholar
  15. 15.
  16. 16.
    Marini, J.C., Forlino, A., Cabral, W.A., et al., Consortium for Osteogenesis Imperfecta Mutations in the Helical Domain of Type I Collagen: Regions Rich in Lethal Mutations Align with Collagen Binding Sites for Integrins and Proteoglycans, Hum. Mutat., 2007, vol. 28, pp. 209–221.PubMedCrossRefGoogle Scholar
  17. 17.
    Witecka, J., Auguoeciak-Duma, A.M., Kruczek, A., and Szydlo, A., Two Novel COL1A1 Mutations in Patients with Osteogenesis Imperfecta (OI) Affect the Stability of the Collagen Type I Triple-Helix, J. Appl. Genet., 2008, vol. 49, no. 3, pp. 283–295.PubMedCrossRefGoogle Scholar
  18. 18.
    Mathew, C.C., The Isolation of High Molecular Weight Eukaryotic DNA, Methods in Molecular Biology, Walker, J.M., Ed., New York: Haman Press, 1984.Google Scholar
  19. 19.
    Orita, M., Jmahana, H., Kanazawa, H., et al., Detection of Polymorphism of Human DNA by Gel Electrophoresis as Single Cell Conformation Polymorphism, Proc. Natl. Acad. Sci. USA, 1989, vol. 86, pp. 2766–2770.PubMedCrossRefGoogle Scholar
  20. 20.
    Koerkkoe, J., Ala-Kokko, L., De Paepe, A., et al., Analysis of the COL1A1 and COL1A2 Genes by PCR Amplification and Scanning by Conformation-Sensitive Gel Electrophoresis Identifies only COL1A1 Mutations in 15 Patients with Osteogenesis Imperfecta Type I: Identification of Common Sequences of Null-Allele Mutations, Am. J. Hum. Genet., 1998, vol. 62, no. 1, pp. 98–110.CrossRefGoogle Scholar
  21. 21.
    Barrett, J.C., Fry, B., Maller, J., and Daly, M.J., Haploview: Analysis and Visualization of LD and Haplo-type Maps, Bioinformatics, 2005, vol. 21, no. 2, pp. 263–265.PubMedCrossRefGoogle Scholar
  22. 22.
    Epstein, M.P. and Satten, G.A., Inference on Haplo-type Effects in Case-Control Studies Using Unphased Genotype Data, Am. J. Hum. Genet., 2003, vol.73, pp. 1316–1329.PubMedCrossRefGoogle Scholar
  23. 23.
  24. 24.
    Ries-Levavi, L., Ish-Shalom, T., Frydman, M., et al., Genetic and Biochemical Analyses of Israeli Osteogenesis Imperfecta Patients, Hum. Mutat., 2004, vol. 23, no. 4, pp. 399–400.PubMedCrossRefGoogle Scholar
  25. 25.
    Roschger, P., Fratzl-Zelman, N., Misof, B.M., et al., Evidence That Abnormal High Bone Mineralization in Growing Children with Osteogenesis Imperfecta Is not Associated with Specific Collagen Mutations, Calcif. Tissue Int., 2008, vol. 82, no. 4, pp. 263–270.PubMedCrossRefGoogle Scholar
  26. 26.
    Willing, M.C., Deschenes, S.P., Slayton, R.L., and Roberts, E.J., Premature Chain Termination Is a Unifying Mechanism for COL1A1 Null Alleles in Osteogenesis Imperfecta Type I Cell Strains, Am. J. Hum. Genet., 1996, vol. 59, no. 4, pp. 799–809.PubMedGoogle Scholar
  27. 27.
    Redford-Badwal, D.A., Stover, M.L., Valli, M., et al., Nuclear Retention of COL1A1 Messenger RNA Identifies Null Alleles Causing Mild Osteogenesis Imperfect, J. Clin. Invest., 1996, vol. 15, pp. 1035–1040.CrossRefGoogle Scholar
  28. 28.
    Reis, F.C., Alexandrino, F., Steiner, C.E., et al., Molecular Findings in Brazilian Patients with Osteogenesis Imperfecta, J. Appl. Genet., 2005, vol. 46, no. 1, pp. 105–108.PubMedGoogle Scholar
  29. 29.
    Pollitt, R., McMahon, R., Nunn, J., et al., Mutation Analysis of COL1A1 and COL1A2 in Patients Diagnosed with Osteogenesis Imperfecta Type I–IV, Hum. Mutat., 2006, vol. 27, no. 7, pp. 716–723.PubMedCrossRefGoogle Scholar
  30. 30.
    Pace, J.M., Chitayat, D., Atkinson, M., et al., A Single Amino Acid Substitution (D1441Y) in the Carboxyl-Terminal Propeptide of the Pro1(I) Chain of Type I Collagen Results in a Lethal Variant of Osteogenesis Imperfecta with Features of Dense Bone Diseases, J. Med. Genet., 2002, vol. 39, pp. 23–29.PubMedCrossRefGoogle Scholar
  31. 31.
    Jin, H., van’t Hof, R.J., Omar, M.E., et al., Promoter and Intron 1 Polymorphisms of COL1A1 Interact to Regulate Transcription and Susceptibility to Osteoporosis, Hum. Mol. Genet., 2009, vol. 15, pp. 2729–2738.CrossRefGoogle Scholar
  32. 32.
    Jin, H., Evangelou, E., Ioannidis, J.P., et al., Polymorphisms in the 5’ Flank of COL1A1 Gene and Osteoporosis: Meta-Analysis of Published Studies, Osteoporos Int., 2011, vol. 22, no. 3, pp. 911–921.PubMedCrossRefGoogle Scholar
  33. 33.
    Selezneva, L.I., Khusainova, R.I., Nurlygaianov, R.Z., et al., Association of Polymorphisms and Haplotypes in the 5 Region of COLIA1 Gene with the Risk of Osteoporotic Fractures in Russian Women from Volga-Ural Region, Russ. J. Genet., 2008, vol. 44, pp. 180–186.CrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2012

Authors and Affiliations

  • D. D. Nadyrshina
    • 1
  • R. I. Khusainova
    • 1
  • E. K. Khusnutdinova
    • 1
    • 2
  1. 1.Institute of Biochemistry and Genetics, Ufa Scientific CenterRussian Academy of SciencesUfaRussia
  2. 2.Department of Genetics and Basic MedicineBashkortostan State UniversityUfaRussia

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