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Eight mutations including 5 novel ones in the COL1A1 gene in Czech patients with osteogenesis imperfecta.

Abstract

BACKGROUND AND AIM

Osteogenesis imperfecta (OI), also called brittle bone disease, is a clinically and genetically heterogeneous disorder characterized by decreased bone density. Autosomal dominant forms result from mutations in either the COL1A1 (collagen type I alpha-1 chain) or COL1A2 (collagen type I alpha-2 chain) genes encoding the type I collagen. The aim of this study was to identify mutations and allelic variants of the COL1A1 gene in patients with osteogenesis imperfecta (OI).

METHODS AND RESULTS

Molecular genetic analysis of the COL1A1 gene was performed in a cohort of 34 patients with OI. The DNA samples were analysed by PCR and Sanger sequencing. DNA changes in coding sequences of the gene were compared with Type 1 Collagen Mutation Database. Genetic variants resulting in either quantitatively or structurally defective protein production were found in 6 unrelated patients. Four identified mutations are connected to decreased protein production (Tyr47X, Arg131X, Arg415X, Gln1341X), 2 result in amino acid substitution (Cys61Phe, Pro1186Ala) and the last affects splicing (c.1057-1G>T). Further, one silent mutation (Gly794Gly) was detected. No protein analysis was performed.

CONCLUSION

Of the 8 identified mutations, 5 were novel and have not been reported before. Only one causes substitution of glycine located within the Gly-X-Y triplets in the triple helical domain. Two mutations are located in major ligand binding regions (MLBR) which are important for bone strength and flexibility. Although the genotype-phenotype correlation is still unclear, our findings should contribute to elucidating this relationship in patients diagnosed with OI.

Authors+Show Affiliations

Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University in Prague, Czech Republic.Centre of Medical Genetics, Antwerp University and University Hospital, Antwerp, Belgium.Centre of Medical Genetics, Antwerp University and University Hospital, Antwerp, Belgium.Ambulant Centre for Defects of Locomotor Apparatus 1.1.c., Prague, Czech Republic. Faculty of Medical Studies, West Bohemia University, Pilsen, Czech Republic.Centre of Medical Genetics, Antwerp University and University Hospital, Antwerp, Belgium.Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University in Prague, Czech Republic.Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University in Prague, Czech Republic.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27132807

Citation

Hruskova, Lucie, et al. "Eight Mutations Including 5 Novel Ones in the COL1A1 Gene in Czech Patients With Osteogenesis Imperfecta." Biomedical Papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia, vol. 160, no. 3, 2016, pp. 442-7.
Hruskova L, Fijalkowski I, Van Hul W, et al. Eight mutations including 5 novel ones in the COL1A1 gene in Czech patients with osteogenesis imperfecta. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2016;160(3):442-7.
Hruskova, L., Fijalkowski, I., Van Hul, W., Marik, I., Mortier, G., Martasek, P., & Mazura, I. (2016). Eight mutations including 5 novel ones in the COL1A1 gene in Czech patients with osteogenesis imperfecta. Biomedical Papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia, 160(3), 442-7. https://doi.org/10.5507/bp.2016.022
Hruskova L, et al. Eight Mutations Including 5 Novel Ones in the COL1A1 Gene in Czech Patients With Osteogenesis Imperfecta. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2016;160(3):442-7. PubMed PMID: 27132807.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Eight mutations including 5 novel ones in the COL1A1 gene in Czech patients with osteogenesis imperfecta. AU - Hruskova,Lucie, AU - Fijalkowski,Igor, AU - Van Hul,Wim, AU - Marik,Ivo, AU - Mortier,Geert, AU - Martasek,Pavel, AU - Mazura,Ivan, Y1 - 2016/04/27/ PY - 2015/11/09/received PY - 2016/04/13/accepted PY - 2016/5/3/entrez PY - 2016/5/3/pubmed PY - 2017/4/19/medline KW - COL1A1 KW - collagen type I KW - mutations KW - osteogenesis imperfecta SP - 442 EP - 7 JF - Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia JO - Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub VL - 160 IS - 3 N2 - BACKGROUND AND AIM: Osteogenesis imperfecta (OI), also called brittle bone disease, is a clinically and genetically heterogeneous disorder characterized by decreased bone density. Autosomal dominant forms result from mutations in either the COL1A1 (collagen type I alpha-1 chain) or COL1A2 (collagen type I alpha-2 chain) genes encoding the type I collagen. The aim of this study was to identify mutations and allelic variants of the COL1A1 gene in patients with osteogenesis imperfecta (OI). METHODS AND RESULTS: Molecular genetic analysis of the COL1A1 gene was performed in a cohort of 34 patients with OI. The DNA samples were analysed by PCR and Sanger sequencing. DNA changes in coding sequences of the gene were compared with Type 1 Collagen Mutation Database. Genetic variants resulting in either quantitatively or structurally defective protein production were found in 6 unrelated patients. Four identified mutations are connected to decreased protein production (Tyr47X, Arg131X, Arg415X, Gln1341X), 2 result in amino acid substitution (Cys61Phe, Pro1186Ala) and the last affects splicing (c.1057-1G>T). Further, one silent mutation (Gly794Gly) was detected. No protein analysis was performed. CONCLUSION: Of the 8 identified mutations, 5 were novel and have not been reported before. Only one causes substitution of glycine located within the Gly-X-Y triplets in the triple helical domain. Two mutations are located in major ligand binding regions (MLBR) which are important for bone strength and flexibility. Although the genotype-phenotype correlation is still unclear, our findings should contribute to elucidating this relationship in patients diagnosed with OI. SN - 1213-8118 UR - https://www.unboundmedicine.com/medline/citation/27132807/Eight_mutations_including_5_novel_ones_in_the_COL1A1_gene_in_Czech_patients_with_osteogenesis_imperfecta_ L2 - http://biomed.papers.upol.cz/doi/10.5507/bp.2016.022.html DB - PRIME DP - Unbound Medicine ER -