Mutations in COL1A1 and COL1A2 Genes Associated with Osteogenesis Imperfecta (OI) Types I or III.

  • Aleksandra Augusciak-Duma Department of Molecular Biology and Genetics School of Medicine in Katowice; Medical University of Silesia, Katowice, Poland
  • Joanna Witecka Department of Molecular Biology and Genetics School of Medicine in Katowice; Medical University of Silesia, Katowice, Poland
  • Aleksander L. Sieroń Department of Molecular Biology and Genetics School of Medicine in Katowice; Medical University of Silesia, Katowice, Poland
  • Magdalena Janeczko Jagiellonian University, Collegium Medicum, Chair of Pediatrics, Department of Medical Genetics, Polish-American Children’s Hospital, Krakow, Poland
  • Jacek J Pietrzyk Jagiellonian University, Collegium Medicum, Chair of Pediatrics, Department of Medical Genetics, Polish-American Children’s Hospital, Krakow, Poland
  • Karolina Ochman Clinics and Medical Laboratories INVICTA, Genetics Clinic, Gdansk, Poland
  • Anna Galicka Department of Medical Chemistry, Medical University of Bialystok, Poland
  • Maria K Borszewska-Kornacka Neonatal and Intensive Care Department Medical University of Warsaw, Warsaw, Poland
  • Jacek Pilch Department of Child Neurology; School of Medicine in Katowice; Medical University of Silesia, Katowice, Poland
  • Elzbieta Jakubowska-Pietkiewicz Department of Pediatric Propedeutics and Bone Metabolism Diseases, Medical University in Lodz, Poland


Over 85% of osteogenesis imperfecta (OI) cases associates to mutations in procollagen type I genes (COL1A1 or COL1A2), however, no hot spots were linked to particular clinical phenotypes. The 8 patients whom were clinically diagnosed with OI are from Polish population with no ethnic background indicated. Six unpublished mutations were detected in eight patients diagnosed with OI. Genotypes for polymorphisms (Sp1 - rs1800012 and PvuII - rs412777), linked to bone formation and metabolism were also determined. In COL1A1 gene the mutations were found in exons 2, 22, 50 and in introns 13 and 51. In COL1A2 one mutation was identified in exon 22. Mutations of deletion type in COL1A1 that resulted in OI type I an effect neither on collagen type I secretion nor its intracellular accumulation were detected. Also, a single base substitution in I13 (c.904-9 G>T) was associated with OI type I. The OI type III was associated with 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 triple helical domain of the collagen type I molecule caused OI type III. It affected secretion of heterotrimeric form of procollagen type I. However, no intracellular accumulation of procollagen chains could be detected. Mutation in COL1A2 affected its incorporation to procollagen type I. The results shall help in genetic counseling of OI patients and provide rational support in making by them and their families conscious, life important decisions.


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