LINKAGE ANALYSIS IN DOMINANTLY INHERITED OSTEOGENESIS IMPERFECTA

The only serious attempts at linkage in osteogenesis imperfecta (OI) have shown that the disease is linked to type 1 collagen genes in all families studied in which it segregrates as a clear mendelian dominant trait. For prenatal diagnosis the probability that a new family is linked can be taken as greater than 0.95 and this figure is augmented as more meioses are studied. Some phenotype correlations, notably between the OI type IV phenotype and linkage to COL1A2 and between presenile hearing loss in OI type I and linkage to COL1A1, can be used to improve risk estimates substantially in families where there are no segregation data to distinguish whether COL1A1 or COL1A2 is the mutant locus.