Biomedical papers, 2016 (vol. 160), issue 3

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2016, 160(3):442-447 | 10.5507/bp.2016.022

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

Lucie Hruskovaa, Igor Fijalkowskib, Wim Van Hulb, Ivo Marikc,d, Geert Mortierb, Pavel Martaseka, Ivan Mazuraa
a Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University in Prague, Czech Republic
b Centre of Medical Genetics, Antwerp University and University Hospital, Antwerp, Belgium
c Ambulant Centre for Defects of Locomotor Apparatus 1.1.c., Prague, Czech Republic
d Faculty of Medical Studies, West Bohemia University, Pilsen, Czech Republic

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.

Keywords: collagen type I, COL1A1, mutations, osteogenesis imperfecta

Received: November 9, 2015; Accepted: April 13, 2016; Prepublished online: April 27, 2016; Published: September 20, 2016


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