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Mutational analysis of COL1A1 and COL1A2 genes among Estonian osteogenesis imperfecta patients
Journal article   Open access   Peer reviewed

Mutational analysis of COL1A1 and COL1A2 genes among Estonian osteogenesis imperfecta patients

L. Zhytnik, K. Maasalu, E. Reimann, E. Prans, S. Kõks and A. Märtson
Human Genomics, Vol.11(1)
2017
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Abstract

Background Osteogenesis imperfecta (OI) is a rare bone disorder. In 90% of cases, OI is caused by mutations in the COL1A1/2 genes, which code procollagen α1 and α2 chains. The main aim of the current research was to identify the mutational spectrum of COL1A1/2 genes in Estonian patients. The small population size of Estonia provides a unique chance to explore the collagen I mutational profile of 100% of OI families in the country. Methods We performed mutational analysis of peripheral blood gDNA of 30 unrelated Estonian OI patients using Sanger sequencing of COL1A1 and COL1A2 genes, including all intron-exon junctions and 5′UTR and 3′UTR regions, to identify causative OI mutations. Results We identified COL1A1/2 mutations in 86.67% of patients (26/30). 76.92% of discovered mutations were located in the COL1A1 (n = 20) and 23.08% in the COL1A2 (n = 6) gene. Half of the COL1A1/2 mutations appeared to be novel. The percentage of quantitative COL1A1/2 mutations was 69.23%. Glycine substitution with serine was the most prevalent among missense mutations. All qualitative mutations were situated in the chain domain of pro-α1/2 chains. Conclusion Our study shows that among the Estonian OI population, the range of collagen I mutations is quite high, which agrees with other described OI cohorts of Northern Europe. The Estonian OI cohort differs due to the high number of quantitative variants and simple missense variants, which are mostly Gly to Ser substitutions and do not extend the chain domain of COL1A1/2 products.

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Citation topics
1 Clinical & Life Sciences
1.132 Extracellular Matrix & Cell Differentiation
1.132.1065 Collagen Disorders
Web Of Science research areas
Genetics & Heredity
ESI research areas
Molecular Biology & Genetics
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