Internal deletion in a collagen gene in a perinatal lethal form of osteogenesis imperfecta

Cloned probes specific for unique genes have proven to be powerful tools in defining the nature of genetic diseases such as the thalassaemias¹ and growth hormone deficiencies². A similar approach should be useful in defining heritable diseases of type I collagen, the heterotrimer of two α1(I) chains and one α2(I) chain, which is the most abundant member of the collagen family of proteins. Recently, cloned cDNAs and genomic DNAs for the two polypeptide chains of the type I collagen^3-10 have become available and have been used to elucidate the chromosomal location of the corresponding genes^11-14. Here, we have used several of these cloned DNAs to demonstrate the presence of an internal deletion of about 0.5 kilobases (kb) in one allele for the proα1(I) chain in a patient with osteogenesis imperfecta (OI), a group of heritable disorders which are characterized by brittle bones but which are highly heterogeneous both phenotypically and biochemically^15,16.