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 thalassaemias and growth hormone deficiencies. A similar approach should be useful in defining heritable diseases of type I collagen, the heterotrimer of two alpha 1(I) chains and one alpha 2(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 have become available and have been used to elucidate the chromosomal location of the corresponding genes. 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 pro alpha 1(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.