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

Abstract

Although over 85% of osteogenesis imperfecta (OI) cases are associated with mutations in the procollagen type I genes (COL1A1 or COL1A2), no hot spots for the mutations were associated with particular clinical phenotypes. Eight patients that were studied here, diagnosed with OI by clinical standards, are from the Polish population with no ethnic background indicated. Previously unpublished mutations were found in six out of those eight patients. Genotypes for polymorphisms (Sp1 - rs1800012 and PvuII - rs412777), linked to bone formation and metabolism were determined. Mutations were found in exons 2, 22, 50 and in introns 13 and 51 of the COL1A1 gene. In COL1A2, one mutation was identified in exon 22. Deletion type mutations in COL1A1 that resulted in OI type I had no effect on collagen type I secretion, nor on its intracellular accumulation. Also, a single base substitution in I13 (c.904-9 G>T) was associated with the OI type I. The OI type III was associated with a 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 the triple helical domain of the collagen type I molecule caused OI type III. It affected secretion of the heterotrimeric form of procollagen type I. However, no intracellular accumulation of procollagen chains could be detected. Mutation in COL1A2 affected its incorporation into procollagen type I. The results obtained shall help in genetic counseling of OI patients and provide a rational support for making informed, life important decisions by them and their families.

Systems biology analysis of osteogenic differentiation behavior by canine mesenchymal stem cells derived from bone marrow and dental pulp

“…Based on cellular component and process analyses, it has been reported that collagen type I alpha 1 (COL1A1) and collagen type I alpha 2 (COL1A2) are proteins which support bone tissues, and mutations of COL1A1 and COL1A2 are related to osteogenesis imperfecta 67 . However, they were downregulated in cBM-MSCs and cDPSCs during an osteogenic induction, while integrin subunit alpha 5 (ITGA5), fibronectin 1 (FN1), and vitronectin (VTN) were upregulated.…”

Prenatal diagnosis of fetal skeletal dysplasia using targeted next-generation sequencing: an analysis of 30 cases

“…Approximately 90% of osteogenesis imperfecta cases are due to causative variants in the COL1A1 and COL1A2 genes, which result in abnormal collagen I fibrils formation, while the remaining 10% of cases are associated with recessive variants of known or yet to be discovered genes [24, 25].…”

Single Nucleotide Polymorphisms in COL1A2 Gene and Dental Fluorosis Among 4 and 8-Year-Old Nigerian Children

“…Sequencing of the COL1A2 PCR product and comparison with the SNP database identified an allele change of an A to a C, at position 1917bp in the COL1A2 gene (resulting in a proline to proline at position 482 on the protein) [25]. This SNP has previously been identified as part of a study investigating osteogenesis imperfecta (OI) types I or III but to our knowledge has not specifically been looked at in relation to fluorosis risk, (rs412777) [26]. The previously identified C to an A SNP at position 1919 (rs414408) was not observed in any of our samples analysed in this population.…”