MOLECULAR HETEROGENEITY IN THE MILD AUTOSOMAL DOMINANT FORMS OF OSTEOGENESIS IMPERFECTA

Abstract

Mild osteogenesis imperfecta (OI type I and OI type IV) is characterized by postnatal onset of fractures, absence of skeletal deformity, presenile hearing loss with or without blue sclerae and dentinogenesis imperfecta. Using 1 common DNA polymorphism associated with the pro.alpha.2(I) human collagen gene, genetic heterogeneity was found in this disorder. In 3 families, the OI phenotype segregated independently of the DNA polymorphism, whereas in 1 family, the OI phenotype cosegregated with a DNA polymorphism in a manner suggesting linkage. Use of DNA polymorphisms associated with both type I procollagen genes should provided a tool to unravel the molecular heterogeneity of various heritable disorders of the connective tissue.