A new recurrent point mutation in the COL1A2 gene was found in a patient with type III osteogenesis imperfecta (OI). A G-to-T transversion in nucleotide position 1121 leads to an amino acid substitution Gly238Cys. This is the first report on the most N-terminal cysteine substitution in COL1A2 reported so far. Until now, at this position, only serine substitutions were observed five times in unrelated patients showing a highly variable expression of OI. It is obvious that endogenic and/or exogenic modifiers are involved in this classical autosomal dominant (or rarely recessive) mendelian disorder. An apparent preferential substitution by cysteine and serine residues is discussed with reference to post-transcriptional or post-translational collagen assembly control.
Amino Acid Substitution Base Sequence