Glycine to tryptophan substitution in type I collagen in a patient with OI type III: a unique collagen mutation
- aCentre for Medical Genetics, OK5, University Hospital Gent, 185 De Pintelaan, B-9000 Gent, Belgium, bInstitute of Child Health, Medical Genetics, University of Istanbul, Istanbul, Turkey
- Dr Nuytinck, Lieve.Nuytinck{at}rug.ac.be
- Revised 12 November 1999
- Accepted 22 December 1999
Abstract
We report a unique glycine substitution in type I collagen and highlight the clinical and biochemical consequences. The proband is a 9 year old Turkish boy with severely deforming osteogenesis imperfecta (OI). Biochemical analysis of (pro) collagen type I from a skin fibroblast culture showed both normal and overmodified α chains. Molecular analysis showed a G>T transversion in theCOL1A2 gene, resulting in the substitution of glycine by tryptophan at position 277 of the α2(I) collagen chain. Glycine substitutions in type I collagen are the most frequent cause of the severe and lethal forms of OI. The phenotypic severity varies according to the nature and localisation of the mutation. Substitutions of glycine by tryptophan, which is the most voluminous amino acid, have not yet been identified in type I collagen or any other fibrillar collagen. The severe, though non-lethal OI phenotype associated with this mutation may appear surprising in view of the huge size of the tryptophan residue. The fact that the mutation resides within a so called “non-lethal” region of the α2(I) collagen chain supports a regional model in phenotypic severity for α2(I) collagen mutations, in which the phenotype is determined primarily by the nature of the collagen domain rather than the type of glycine substitution involved.
