Valencia, María2; Caparrós-Martin, Jose A2; Sirerol-Piquer, María Salomé2; García-Verdugo, José Manuel2; Martínez-Glez, Víctor2; Lapunzina, Pablo2; Temtamy, Samia2; Aglan, Mona2; Lund, Allan M1; Nikkels, Peter G J2; Ruiz-Perez, Victor L2; Ostergaard, Elsebet1
1 Klinisk Genetisk Klinik, Juliane Marie Centre, Rigshospitalet, The Capital Region of Denmark2 unknown
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.
American Journal of Medical Genetics. Part a, 2014, Vol 164A, Issue 5, p. 1143-50