Identification andIn VivoFunctional Characterization of Novel Compound HeterozygousBMP1Variants in Osteogenesis Imperfecta
- 17 November 2014
- journal article
- research article
- Published by Hindawi Limited in Human Mutation
- Vol. 36 (2) , 191-195
Abstract
Osteogenesis imperfecta (OI) comprises a heterogeneous group of disorders that are characterized by susceptibility to bone fractures, and range in severity from a subtle increase in fracture frequency to death in the perinatal period. Most patients have defects in type I collagen biosynthesis with autosomal‐dominant inheritance, but many autosomal‐recessive genes have been reported. We applied whole‐exome sequencing to identify mutations in a Korean OI patient who had an umbilical hernia, frequent fractures, a markedly short stature, delayed motor development, scoliosis, and dislocation of the radial head, with a bowed radius and ulna. We identified two novel variants in the BMP1 gene: c.808A>G and c.1297G>T. The former variant caused a missense change p.(Met270Val) and the latter variant caused the skipping of exon 10. The hypofunctional nature of the two variants was demonstrated in a zebrafish assay.Keywords
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