TY - JOUR
T1 - Report of a newly indentified patient with mutations in BMP1 and underlying pathogenetic aspects
AU - Valencia, María
AU - Caparrós-Martin, Jose A
AU - Sirerol-Piquer, María Salomé
AU - García-Verdugo, José Manuel
AU - Martínez-Glez, Víctor
AU - Lapunzina, Pablo
AU - Temtamy, Samia
AU - Aglan, Mona
AU - Lund, Allan M
AU - Nikkels, Peter G J
AU - Ruiz-Perez, Victor L
AU - Ostergaard, Elsebet
N1 - © 2014 Wiley Periodicals, Inc.
PY - 2014/5
Y1 - 2014/5
N2 - 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.
AB - 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.
U2 - 10.1002/ajmg.a.36427
DO - 10.1002/ajmg.a.36427
M3 - Journal article
C2 - 24648371
SN - 1552-4825
VL - 164A
SP - 1143
EP - 1150
JO - American Journal of Medical Genetics. Part A
JF - American Journal of Medical Genetics. Part A
IS - 5
ER -