Report of a newly indentified patient with mutations in BMP1 and underlying pathogenetic aspects

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-e...

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Main Authors: Valencia, M., Caparrós-Martín, Jose, Sirerol-Piquer, M., García-Verdugo, J., Martínez-Glez, V., Lapunzina, P., Temtamy, S., Aglan, M., Lund, A., Nikkels, P., Ruiz-Perez, V., Ostergaard, E.
Format: Journal Article
Published: John Wiley & Sons, Inc. 2014
Online Access:http://hdl.handle.net/20.500.11937/68226
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author Valencia, M.
Caparrós-Martín, Jose
Sirerol-Piquer, M.
García-Verdugo, J.
Martínez-Glez, V.
Lapunzina, P.
Temtamy, S.
Aglan, M.
Lund, A.
Nikkels, P.
Ruiz-Perez, V.
Ostergaard, E.
author_facet Valencia, M.
Caparrós-Martín, Jose
Sirerol-Piquer, M.
García-Verdugo, J.
Martínez-Glez, V.
Lapunzina, P.
Temtamy, S.
Aglan, M.
Lund, A.
Nikkels, P.
Ruiz-Perez, V.
Ostergaard, E.
author_sort Valencia, M.
building Curtin Institutional Repository
collection Online Access
description 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. © 2014 Wiley Periodicals, Inc.
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spelling curtin-20.500.11937-682262018-05-18T08:07:20Z Report of a newly indentified patient with mutations in BMP1 and underlying pathogenetic aspects Valencia, M. Caparrós-Martín, Jose Sirerol-Piquer, M. García-Verdugo, J. Martínez-Glez, V. Lapunzina, P. Temtamy, S. Aglan, M. Lund, A. Nikkels, P. Ruiz-Perez, V. Ostergaard, E. 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. © 2014 Wiley Periodicals, Inc. 2014 Journal Article http://hdl.handle.net/20.500.11937/68226 10.1002/ajmg.a.36427 John Wiley & Sons, Inc. restricted
spellingShingle Valencia, M.
Caparrós-Martín, Jose
Sirerol-Piquer, M.
García-Verdugo, J.
Martínez-Glez, V.
Lapunzina, P.
Temtamy, S.
Aglan, M.
Lund, A.
Nikkels, P.
Ruiz-Perez, V.
Ostergaard, E.
Report of a newly indentified patient with mutations in BMP1 and underlying pathogenetic aspects
title Report of a newly indentified patient with mutations in BMP1 and underlying pathogenetic aspects
title_full Report of a newly indentified patient with mutations in BMP1 and underlying pathogenetic aspects
title_fullStr Report of a newly indentified patient with mutations in BMP1 and underlying pathogenetic aspects
title_full_unstemmed Report of a newly indentified patient with mutations in BMP1 and underlying pathogenetic aspects
title_short Report of a newly indentified patient with mutations in BMP1 and underlying pathogenetic aspects
title_sort report of a newly indentified patient with mutations in bmp1 and underlying pathogenetic aspects
url http://hdl.handle.net/20.500.11937/68226