A GLY238SER SUBSTITUTION IN THE ALPHA-2 CHAIN OF TYPE-I COLLAGEN RESULTS IN OSTEOGENESIS IMPERFECTA TYPE-III

In general, osteogenesis imperfecta (brittle bone disease) is caused b y heterozygous mutations in the genes encoding the alpha 1 or alpha 2 chains of type I collagen (COL1A1 and COL1A2, respectively). In this s tudy we screened these genes in a proband presenting with the severe f orm (type III) of osteogenesis imperfecta for mutations which might re sult in the phenotype. Single-strand conformation polymorphism mapping analysis was used to identify a region suspected of harbouring the mu tation and subsequent sequence analysis revealed a heterozygous G to A transition in the alpha 2(I) gene of type I collagen in the individua l. The resulting substitution of the glycine at position 238 of the al pha chain by serine is the most N-terminal yet reported for this chain .