Variable clinical expression in a family with OI type IV due to deletion of three base pairs in COL1A1

We have studied a family with autosomal dominant osteogenesis imperfecta (OI) type IV. Electrophoresis of collagen produced by cultured fibroblasts revealed a slower migrating population of collagen I. Cyanogen bromide peptide mapping localised the structural defect to the area of the alpha 1(1)CB3 peptide. Subsequent sequencing revealed a deletion of nucleotides 1964-1966 in exon 27 of COLlA1. By means of restriction enzyme analysis, the deletion could be detected in all affected family members. This in-frame deletion resulted in the removal of alanine-438 and a Glu437Asp substitution in the proal(I) collagen chain. Clinical variation was considerable among affected family members. The most consistent clinical features were reduced height and extraosseous manifestations of OI.