Abstract
BackgroundMutations in the FKBP10 gene were first described in patients with Osteogenesis imperfecta type III. Two follow up reports found FKBP10 mutations to be associated with Bruck syndrome type 1, a rare disorder characterized by congenital contractures and bone fragility. This raised the question if the patients in the first report indeed had isolated Osteogenesis imperfecta or if Bruck syndrome would have been the better diagnosis.MethodsThe patients described here are affected by severe autosomal recessive Osteogenesis imperfecta without contractures.ResultsHomozygosity mapping identified FKBP10 as a candidate gene, and sequencing revealed a base pair exchange that causes a C-terminal premature stop codon in this gene.ConclusionsOur study demonstrates that FKBP10 mutations not only cause Bruck syndrome or Osteogenesis imperfecta type III but can result in a severe type of isolated Osteogenesis imperfecta type IV with prenatal onset. Furthermore, it adds dentinogenesis imperfecta to the spectrum of clinical symptoms associated with FKBP10 mutations.
Highlights
Mutations in the FK506-binding protein (FKBP10) gene were first described in patients with Osteogenesis imperfecta type III
The disorder is characterized by bone fragility that varies in severity between the different Osteogenesis imperfecta (OI) subtypes
Homozygosity for mutations in CRTAP, LEPRE1, PPIB, or OSTERIX has been shown to cause mostly severe types of OI that result from overmodification of procollagen chains and their retention in the rough endoplasmatic reticulum (rER) [2,3,4,5,6,7]
Summary
Mutations in the FKBP10 gene were first described in patients with Osteogenesis imperfecta type III. Two follow up reports found FKBP10 mutations to be associated with Bruck syndrome type 1, a rare disorder characterized by congenital contractures and bone fragility. This raised the question if the patients in the first report had isolated Osteogenesis imperfecta or if Bruck syndrome would have been the better diagnosis. Even rarer than the dominant disorders are the autosomal recessive forms of OI for which several genes are known . These genes are mainly involved in the processing, assembly and trafficking of procollagen chains, a multi-step process that involves a large number of critical post-translational modifications. Autosomal recessive brittle bone disease without procollagen overmodification can be caused by mutations in either SERPINH1 or FKBP10 genes that encode the collagen
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