A novel splicing mutation in FKBP10 causing osteogenesis imperfecta with a possible mineralization defect

Bone. 2012 Jan;50(1):343-9. doi: 10.1016/j.bone.2011.10.023. Epub 2011 Oct 30.

Abstract

Osteogenesis imperfecta (OI) is a group of hereditary disorders characterized by bone fragility and osteopenia, with a broad spectrum of clinical severity. The majority of cases are dominantly inherited and due to mutations in type I collagen genes, whereas recessive forms are less frequent and attributable to mutations in different genes involved in collagen I post translational modifications and folding (prolyl-3-hydroxylase complex, SERPINH1, FKBP10). We report the case of a patient with an initially mild and then progressively severe form of osteogenesis imperfecta due to a novel homozygous splicing mutation in FKBP10 (intron 8 c.1399+1G>A), which results in aberrant mRNA processing and consequent lack of FKBP65 chaperone. Although this mutation does not affect collagen type I post translational modifications in dermal fibroblasts, the histomorphometric pattern of our patient's bone sample showed a mineralization defect possibly due to the mutation in FKBP10.

Publication types

  • Case Reports

MeSH terms

  • Calcification, Physiologic / genetics*
  • Child
  • Child, Preschool
  • Collagen Type I / genetics
  • Collagen Type I / metabolism
  • Collagen Type I, alpha 1 Chain
  • DNA Mutational Analysis
  • Humans
  • Male
  • Mutation*
  • Osteogenesis Imperfecta / genetics*
  • Osteogenesis Imperfecta / pathology
  • Osteogenesis Imperfecta / physiopathology
  • Osteogenesis Imperfecta / therapy
  • RNA Splicing*
  • Tacrolimus Binding Proteins / genetics*

Substances

  • Collagen Type I
  • Collagen Type I, alpha 1 Chain
  • Tacrolimus Binding Proteins
  • FKBP10 protein, human