Use of molecular haplotypes specific for the human proα2(I) collagen gene in linkage analysis of the mild autosomal dominant forms of osteogenesis imperfecta

Autosomal dominant osteogenesis imperfecta (OI) is a heterogeneous group of disorders. Molecular haplotypes associated with the proα2(I) gene of human type I procollagen were used for genetic linkage studies in a group of 10 families with OI. The clinical phenotypes of the families studied were those of OI type I and OI type IV. Evidence for linkage was highly suggestive in the four families with OI type IV (Z = 3.91 for θ = 0). In contrast, little or no indication for linkage was found in the six families with OI type I (Z = .055 for θ = .415). Heterogeneity between the two groups of families was highly significant (χ² = 11.14, P = .0008), suggesting that at least two separate gene defects may be the cause of the autosomal dominant forms of OI.