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Two novel COL1A1 mutations in patients with osteogenesis imperfecta (OI) affect the stability of the collagen type I triple-helix.
J Appl Genet. 2008; 49(3):283-95.JA

Abstract

Osteogenesis imperfecta (OI) is a bone dysplasia caused by mutations in the COL1A1 and COL1A2 genes. Although the condition has been intensely studied for over 25 years and recently over 800 novel mutations have been published, the relation between the location of mutations and clinical manifestation is poorly understood. Here we report missense mutations in COL1A1 of several OI patients. Two novel mutations were found in the D1 period. One caused a substitution of glycine 200 by valine at the N-terminus of D1 in OI type I/IV, lowering collagen stability by 50% at 34 degrees C. The other one was a substitution of valine 349 by phenylalanine at the C-terminus of D1 in OI type I, lowering collagen stability at 37.5 degrees C. Two other mutations, reported before, changed amino residues in D4. One was a lethal substitution changing glycine 866 to serine in genetically identical twins with OI type II. That mutated amino acid was near the border of D3 and D4. The second mutation changed glycine 1040 to serine located at the border of D4 and D0.4, in a proband manifesting OI type III, and lowered collagen stability at 39 degrees C (2 degrees C lower than normal). Our results confirm the hypothesis on a critical role of the D1 and D4 regions in stabilization of the collagen triple-helix. The defect in D1 seemed to produce a milder clinical type of OI, whereas the defect in the C-terminal end of collagen type caused the more severe or lethal types of OI.

Authors+Show Affiliations

Department of General and Molecular Biology and Genetics, Medical University of Silesia, Katowice, Poland.No 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)

Case Reports
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18670065

Citation

Witecka, Joanna, et al. "Two Novel COL1A1 Mutations in Patients With Osteogenesis Imperfecta (OI) Affect the Stability of the Collagen Type I Triple-helix." Journal of Applied Genetics, vol. 49, no. 3, 2008, pp. 283-95.
Witecka J, Auguściak-Duma AM, Kruczek A, et al. Two novel COL1A1 mutations in patients with osteogenesis imperfecta (OI) affect the stability of the collagen type I triple-helix. J Appl Genet. 2008;49(3):283-95.
Witecka, J., Auguściak-Duma, A. M., Kruczek, A., Szydło, A., Lesiak, M., Krzak, M., Pietrzyk, J. J., Männikkö, M., & Sieroń, A. L. (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(3), 283-95. https://doi.org/10.1007/BF03195625
Witecka J, et al. Two Novel COL1A1 Mutations in Patients With Osteogenesis Imperfecta (OI) Affect the Stability of the Collagen Type I Triple-helix. J Appl Genet. 2008;49(3):283-95. PubMed PMID: 18670065.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Two novel COL1A1 mutations in patients with osteogenesis imperfecta (OI) affect the stability of the collagen type I triple-helix. AU - Witecka,Joanna, AU - Auguściak-Duma,Aleksandra M, AU - Kruczek,Anna, AU - Szydło,Anna, AU - Lesiak,Marta, AU - Krzak,Maria, AU - Pietrzyk,Jacek J, AU - Männikkö,Minna, AU - Sieroń,Aleksander L, PY - 2008/8/2/pubmed PY - 2008/10/24/medline PY - 2008/8/2/entrez SP - 283 EP - 95 JF - Journal of applied genetics JO - J Appl Genet VL - 49 IS - 3 N2 - Osteogenesis imperfecta (OI) is a bone dysplasia caused by mutations in the COL1A1 and COL1A2 genes. Although the condition has been intensely studied for over 25 years and recently over 800 novel mutations have been published, the relation between the location of mutations and clinical manifestation is poorly understood. Here we report missense mutations in COL1A1 of several OI patients. Two novel mutations were found in the D1 period. One caused a substitution of glycine 200 by valine at the N-terminus of D1 in OI type I/IV, lowering collagen stability by 50% at 34 degrees C. The other one was a substitution of valine 349 by phenylalanine at the C-terminus of D1 in OI type I, lowering collagen stability at 37.5 degrees C. Two other mutations, reported before, changed amino residues in D4. One was a lethal substitution changing glycine 866 to serine in genetically identical twins with OI type II. That mutated amino acid was near the border of D3 and D4. The second mutation changed glycine 1040 to serine located at the border of D4 and D0.4, in a proband manifesting OI type III, and lowered collagen stability at 39 degrees C (2 degrees C lower than normal). Our results confirm the hypothesis on a critical role of the D1 and D4 regions in stabilization of the collagen triple-helix. The defect in D1 seemed to produce a milder clinical type of OI, whereas the defect in the C-terminal end of collagen type caused the more severe or lethal types of OI. SN - 1234-1983 UR - https://www.unboundmedicine.com/medline/citation/18670065/Two_novel_COL1A1_mutations_in_patients_with_osteogenesis_imperfecta__OI__affect_the_stability_of_the_collagen_type_I_triple_helix_ L2 - https://dx.doi.org/10.1007/BF03195625 DB - PRIME DP - Unbound Medicine ER -