Report of a newly indentified patient with mutations in BMP1 and underlying pathogenetic aspects.
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| 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.
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| Authors | María Valencia, Jose A Caparrós-Martin, María Salomé Sirerol-Piquer, José Manuel García-Verdugo, Víctor Martínez-Glez, Pablo Lapunzina, Samia Temtamy, Mona Aglan, Allan M Lund, Peter G J Nikkels, Victor L Ruiz-Perez, Elsebet Ostergaard |
| Journal | American journal of medical genetics. Part A (Am J Med Genet A) Vol. 164A Issue 5 Pg. 1143-50 (May 2014) ISSN: 1552-4833 [Electronic] United States |
| PMID | 24648371 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't) |
| Copyright | © 2014 Wiley Periodicals, Inc. |
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