DIRECT SEQUENCING OF PCR PRODUCTS DERIVED FROM CDNAS FOR THE PRO-ALPHA-1 AND PRO-ALPHA-2 CHAINS OF TYPE-I PROCOLLAGEN AS A SCREENING METHODTO DETECT MUTATIONS IN PATIENTS WITH OSTEOGENESIS IMPERFECTA

More than 150 mutations in the genes for type I procollagen have been found in unrelated patients with osteogenesis imperfecta (OI), but mut ations have been difficult to define in many patients with the mildest forms of the disease. Here, we have used robotically automated sequen cing of the cDNAs for type I procollagen to screen for mutations in 12 patients suspected of having nonlethal OI (types I, III, and IV). Sin gle base mutations that changed codons for obligate glycine residues w ere found in seven of the patients. Altogether, we analyzed 4,379 bp o f sequences of both alleles of the pro alpha 1(I) collagen (8,758 bp o f allelic sequences) and 4,200 bp of sequences of both alleles of the pro alpha 2(I) collagen (8,400 bp of allelic) from each patient. (C) 1 996 Wiley-Liss, Inc.