Reference : Mutation analysis of coding sequences for type I procollagen in individuals with low ...
Scientific journals : Article
Human health sciences : Endocrinology, metabolism & nutrition
Mutation analysis of coding sequences for type I procollagen in individuals with low bone density.
Spotila, L. D. [> > > >]
Colige, Alain mailto [Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Laboratoire des tissus conjonctifs >]
Sereda, L. [> > > >]
Constantinou-Deltas, C. D. [> > > >]
Whyte, M. P. [> > > >]
Riggs, B. L. [> > > >]
Shaker, J. L. [> > > >]
Spector, T. D. [> > > >]
Hume, E. [> > > >]
Olsen, N. [> > > >]
Journal of Bone and Mineral Research
American Society for Bone and Mineral Research
Yes (verified by ORBi)
[en] Adolescent ; Adult ; Aged ; Base Sequence ; Bone Density/genetics ; Bone Diseases, Metabolic/genetics ; Child ; Collagen/chemistry/genetics ; Culture Techniques ; Female ; Humans ; Male ; Middle Aged ; Molecular Sequence Data ; Mutation ; Nucleic Acid Hybridization ; Osteogenesis Imperfecta/genetics ; Osteoporosis/genetics ; Polymerase Chain Reaction ; Polymorphism, Genetic
[en] Mutations in one of the two genes encoding type I procollagen (COL1A1 and COL1A2) are frequently the cause of osteogenesis imperfecta (OI), a disorder characterized by brittle bones. Here we tested whether patients with low bone density also have mutations in these genes. The 26 patients studied had no apparent metabolic bone disease, but most had a positive family history of osteopenia or osteoporosis. Although a diagnosis of OI was considered by the clinician in some cases, the clinical criteria for OI were not satisfied. Our strategy for mutation analysis consisted of PCR amplification of cDNA made to fibroblast mRNA using primers specific for the coding regions of COL1A1 and COL1A2. The PCR products were then sequenced directly with primers located within each PCR product. We found that 3 of 26 patients had mutations that altered the encoded amino acid. One mutation, at position alpha 2(I)-661 has been reported (Spotila et al. 1991 Proc Natl Acad Sci USA PNAS 88:5423). The other 2 patients, who were not related to each other, had a mutation that altered the proline codon at alpha 1(I)-27 to alanine. This mutation was not found in 81 normal individuals or in 37 additional osteopenic individuals. However, its effect on the biologic function of type I collagen, as well as its role in osteopenia, is uncertain. In addition to the two mutations, we found a polymorphism in codon alpha 2(I)-459. Although this polymorphism involved an amino acid substitution, it was present with equal frequency in the patient and the normal population. By analyzing this and previously reported neutral sequence variants in the COL1A2 gene, we determined that all patients expressed both alleles of the COL1A2 gene. The 12 patients who were heterozygous for a COL1A1 neutral sequence variant also expressed both alleles. Here we present all PCR primer and sequencing primer information. The results suggest that surveying a larger group of similarly selected individuals may reveal additional mutations in the COL1A1 or COL1A2 genes.

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