VARIABLE CLINICAL EXPRESSION IN A FAMILY WITH OI TYPE-IV DUE TO DELETION OF 3 BASE-PAIRS IN COL1A1

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