A frameshift mutation results in a truncated nonfunctional carboxyl-terminal Proα1(I) propeptide of type I collagen in osteogenesis imperfecta

Abstract

A codon frameshift mutation caused by a single base (U) insertion after base pair 4088 of preproα1(I) mRNA of type I procollagen was identified in a baby with lethal perinatal osteogenesis imperfecta. The mutation was identified in fibroblast RNA by a new method that allows the direct detection of mismatched bases by chemical modification and cleavage in heteroduplexes formed between mRNA and control cDNA probes. The region of mismatches was specifically amplified by the polymerase chain reaction and sequenced. The heterozygous mutation in the amplified cDNA most likely resulted from a T insertion in exon 49 of COL1A1. The frameshift resulted in a truncated proα1(I) carboxyl-terminal propept..