title: Report of a newly indentified patient with mutations in BMP1 and underlying pathogenetic aspects.
abstract: Osteogenesis imperfecta is a genetic condition characterized by bone fragility and recurrent fractures, which in the large majority of patients are caused by defects in the production of type I collagen. Mutations in the gene encoding bone morphogenetic protein 1 (BMP1, also known as procollagen C-endopeptidase) have been associated with osteogenesis imperfecta in two sib pairs. In this report, we describe an additional patient with osteogenesis imperfecta with normal bone density and a recurrent, homozygous c.34G>C mutation in BMP1. Western blot analysis of dermal fibroblasts from this patient showed decreased protein levels of the two alternatively spliced products of BMP1 and abnormal cleavage of the C-terminal propeptide of type I procollagen. In addition, fluorescence and electron microscopy showed impaired assembly of type I collagen fibrils in the extracellular matrix of cultured fibroblasts derived from two patients: the patient described here and a previously reported patient with a homozygous BMP1 c.747C>G mutation. We conclude that BMP1 is essential for human type I collagen fibrilogenesis.
authors.affiliation: Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Valencia
authors.forename: Jose A
authors.initials: JA
authors.lastname: Caparrós-Martin
authors.forename: María Salomé
authors.initials: MS
authors.lastname: Sirerol-Piquer
authors.forename: José Manuel
authors.initials: JM
authors.lastname: García-Verdugo
authors.forename: Víctor
authors.initials: V
authors.lastname: Martínez-Glez
authors.forename: Pablo
authors.initials: P
authors.lastname: Lapunzina
authors.forename: Samia
authors.initials: S
authors.lastname: Temtamy
authors.forename: Mona
authors.initials: M
authors.lastname: Aglan
authors.forename: Allan M
authors.initials: AM
authors.lastname: Lund
authors.forename: Peter G J
authors.initials: PG
authors.lastname: Nikkels
authors.forename: Victor L
authors.initials: VL
authors.lastname: Ruiz-Perez
authors.forename: Elsebet
authors.initials: E
authors.lastname: Ostergaard
mesh_terms: D015519:Bone Density; D055395:Bone Morphogenetic Protein 1 / Q000235:genetics*; D001842:Bone and Bones / Q000000981:diagnostic imaging; D024042:Collagen Type I / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D010013:Osteogenesis Imperfecta / Q000175:diagnosis* / Q000235:genetics*; D010641:Phenotype; D011859:Radiography
chemical_list: D024042:Collagen Type I; D055395:Bone Morphogenetic Protein 1
keywords: BMP1; bone development; extracellular matrix; osteogenesis imperfecta; type I collagen