These authors contributed equally to this work.
Mutations in PLOD2 cause autosomal-recessive connective tissue disorders within the Bruck syndrome—Osteogenesis imperfecta phenotypic spectrum†
Article first published online: 5 JUL 2012
© 2012 Wiley Periodicals, Inc.
Volume 33, Issue 10, pages 1444–1449, October 2012
How to Cite
Puig-Hervás, M. T., Temtamy, S., Aglan, M., Valencia, M., Martínez-Glez, V., Ballesta-Martínez, M. J., López-González, V., Ashour, A. M., Amr, K., Pulido, V., Guillén-Navarro, E., Lapunzina, P., Caparrós-Martín, J. A. and Ruiz-Perez, V. L. (2012), Mutations in PLOD2 cause autosomal-recessive connective tissue disorders within the Bruck syndrome—Osteogenesis imperfecta phenotypic spectrum. Hum. Mutat., 33: 1444–1449. doi: 10.1002/humu.22133
Communicated by Raymond Dalgleish
- Issue published online: 13 SEP 2012
- Article first published online: 5 JUL 2012
- Accepted manuscript online: 11 JUN 2012 10:21AM EST
- Manuscript Accepted: 23 MAY 2012
- Manuscript Received: 23 FEB 2012
- The Spanish Ministry of Science and Innovation. Grant Number: SAF2010-17901
- The Centro de Investigación Biomédica en Red de Enfermedades Raras Programa de Investigación de Enfermedades Pediátricas
- Bruck syndrome;
- osteogenesis imperfecta;
- Lysyl hydroxylase 2;
- type I collagen
PLOD2 and FKBP10 are genes mutated in Bruck syndrome (BS), a condition resembling osteogenesis imperfecta (OI), but that is also typically associated with congenital joint contractures. Herein, we sought mutations in six consanguineous BS families and detected changes in either PLOD2 or FKBP10 in all cases. Two probands were found with a homozygous frameshift mutation in the alternative exon 13a of PLOD2, indicating that specific inactivation of the longer protein isoform encoded by this gene is sufficient to cause BS. In addition, by homozygosity mapping, followed by a candidate gene approach, we identified a homozygous donor splice site mutation in PLOD2 in a patient with autosomal-recessive OI (AR-OI). Screening of additional samples also revealed compound heterozygous mutations in PLOD2 in two brothers, one affected with mild AR-OI and the other with mild BS. Thus, PLOD2 in addition to causing BS is also associated with AR-OI phenotypes of variable severity. Hum Mutat 33:1444–1449, 2012. © 2012 Wiley Periodicals, Inc.