ZFIN ID: ZDB-PUB-141118-2
Identification and in vivo functional characterization of novel compound heterozygous BMP1 variants in osteogenesis imperfecta
Cho, S.Y., Asharani, P.V., Kim, O.H., Iida, A., Miyake, N., Matsumoto, N., Nishimura, G., Ki, C.S., Hong, G., Kim, S.J., Sohn, Y.B., Park, S.W., Lee, J., Kwun, Y., Carney, T.J., Huh, R., Ikegawa, S., Jin, D.K.
Date: 2015
Source: Human Mutation   36(2): 191-5 (Journal)
Registered Authors: Carney, Tom
Keywords: BMP1, mutation, osteogenesis imperfecta, whole exome sequencing, zebrafish
MeSH Terms:
  • Amino Acid Substitution
  • Animals
  • Bone Morphogenetic Protein 1/genetics*
  • Female
  • Genetic Association Studies
  • Heterozygote
  • Humans
  • Infant
  • Osteogenesis Imperfecta/genetics*
  • Polymorphism, Single Nucleotide
  • Zebrafish
PubMed: 25402547 Full text @ Hum. Mutat.
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 hypo-functional nature of the two variants was demonstrated in a zebrafish assay. This article is protected by copyright. All rights reserved.