Osteoporosis Caused by Mutations in PLS3: Clinical and Bone Tissue Characteristics
Open Access
- 24 February 2014
- journal article
- case report
- Published by Oxford University Press (OUP) in Journal of Bone and Mineral Research
- Vol. 29 (8), 1805-1814
- https://doi.org/10.1002/jbmr.2208
Abstract
Mutations in PLS3 have been identified as a cause of bone fragility in children, but the bone phenotype associated with PLS3 mutations has not been reported in detail. PLS3 is located on the X chromosome and encodes the actin‐binding protein plastin 3. Here we describe skeletal findings in 4 boys from 2 families with mutations in PLS3 (c.994_995delGA; p.Asp332* in family 1; c.1433T > C; p.Leu478Pro in family 2). When first evaluated between 4 and 8 years of age, these boys had a history of one to four long‐bone fractures. Mild vertebral compression fractures were identified in each boy. No obvious extraskeletal disease manifestations were present. Lumbar spine areal bone mineral density (LS‐aBMD) Z‐scores ranged from –1.7 to –3.5, but height was normal. Iliac bone histomorphometry in 2 patients showed low trabecular bone volume and a low osteoid maturation time but normal bone formation rate and osteoclast surface. Quantitative backscattered electron imaging (qBEI) did not reveal a major abnormality in bone mineralization density distribution. The 2 boys from family 1 received oral alendronate for 6 years, which normalized LS‐aBMD. The mothers of the 4 boys did not have a history of fractures and had normal LS‐aBMD. However, one of these mothers had low bone mass at the distal radius, as measured by peripheral quantitative computed tomography (pQCT). In conclusion, hemizygous mutations in PLS3 are associated with osteoporosis and bone fragility in childhood, but in contrast to bone fragility caused by mutations in collagen type I encoding genes, there is no hypermineralization of mineralized bone matrix. © 2014 American Society for Bone and Mineral Research.Keywords
This publication has 41 references indexed in Scilit:
- Attenuated BMP1 Function Compromises Osteogenesis, Leading to Bone Fragility in Humans and ZebrafishAmerican Journal of Human Genetics, 2012
- Plastin Family of Actin-Bundling Proteins: Its Functions in Leukocytes, Neurons, Intestines, and CancerInternational Journal of Cell Biology, 2012
- New perspectives on osteogenesis imperfectaNature Reviews Endocrinology, 2011
- ANNOVAR: functional annotation of genetic variants from high-throughput sequencing dataNucleic Acids Research, 2010
- A method and server for predicting damaging missense mutationsNature Methods, 2010
- Genotype–phenotype correlations in nonlethal osteogenesis imperfecta caused by mutations in the helical domain of collagen type IEuropean Journal of Human Genetics, 2010
- The Sequence Alignment/Map format and SAMtoolsBioinformatics, 2009
- Fast and accurate short read alignment with Burrows–Wheeler transformBioinformatics, 2009
- High-resolution cryo-EM structure of the F-actin–fimbrin/plastin ABD2 complexProceedings of the National Academy of Sciences of the United States of America, 2008
- UCSF Chimera?A visualization system for exploratory research and analysisJournal of Computational Chemistry, 2004