Background: Osteogenesis imperfecta (OI) includes a group of disorders with a susceptibility to bone fractures, the presentation ranging from slightly increased fracture frequency to death in the perinatal period.
Objective and hypotheses: Autosomal-dominant inheritance with type I collagen biosynthesis defects is the most common, but many autosomal-recessive genes have been previously reported.
Method: Whole-exome sequencing was performed to simultaneously examine multiple genes associated with autosomal-recessive OI in a Korean patient with umbilical hernia, frequent fractures, scoliosis, markedly short stature and dislocation of the radial head.
Results: Two novel variants in the BMP1 gene: c.808A>G and c.1297G>T were identified. The former variant caused a missense change p.(Met270Val) and the latter caused skipping of exon 10. Functional studies of the two variants demonstrated in a zebrafish assay showed a hypofunctional nature.
Conclusion: Demonstration of hypofunction of the two novel variants in zebrafish supports the involvement of these variants in causing abnormal bones. These results emphasise the importance of BMP1 as a contributing factor in autosomal-recessive OI.
01 - 03 Oct 2015
European Society for Paediatric Endocrinology