title: A novel splicing mutation in FKBP10 causing osteogenesis imperfecta with a possible mineralization defect.
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.
authors: Department of Life and Reproduction Sciences, Pediatric Clinic, University of Verona, Italy.
authors: Giacomo
authors: G
authors: Venturi
authors: Elena
authors: E
authors: Monti
authors: Luca
authors: L
authors: Dalle Carbonare
authors: Massimiliano
authors: M
authors: Corradi
authors: Alberto
authors: A
authors: Gandini
authors: Maria Teresa
authors: MT
authors: Valenti
authors: Attilio
authors: A
authors: Boner
authors: Franco
authors: F
authors: Antoniazzi
mesh_terms: D002113:Calcification, Physiologic / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D000090602:Collagen Type I, alpha 1 Chain; D004252:DNA Mutational Analysis; D006801:Humans; D008297:Male; D009154:Mutation; D010013:Osteogenesis Imperfecta / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D012326:RNA Splicing; D022021:Tacrolimus Binding Proteins / Q000235:genetics*
chemical_list: D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D022021:Tacrolimus Binding Proteins; C110054:FKBP10 protein, human