Co-occurrence of heterozygous mutations in and in a high-risk pregnancy complicated by osteogenesis imperfecta.

Mutations in several genes, including and , have been associated with the development of osteogenesis imperfecta (OI). Here, we reported the co-occurrence of a rare heterozygous variant (c.167C>G p.Ala56Gly) in and a novel heterozygous mutation (c.1634G>A p.Gly545Asp) in in a foetus with a severe form of OI. Bioinformatics modelling revealed that the effect of the mutation on is neutral. In contrast, the mutation in is deleterious. It is predicted to cause distortion of the α (1) chain of the type I collagen and results in structural instability of the protein. Therefore, a novel dominant variant of likely underlies the severe foetal pathology observed, although we do not exclude the possibility that the heterozygous mutations in and may interact and co-ordinately cause pathogenesis. This novel mutation is recommended to be included in the diagnostic panels for OI.