Peter Kannu1, Areej Mahjoub2, Riyana Babul-Hirji1, Melissa T Carter3, Jennifer Harrington4. 1. Department of Pediatrics, Division of Clinical and Metabolic Genetics, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada. 2. Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada. 3. Regional Genetics Program, Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, Ontario, Canada. 4. Department of Pediatrics, Division of Endocrinology, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
Abstract
BACKGROUND AND OBJECTIVES: Plastin 3 (PLS3) mutations are associated with an X-linked osteoporosis. Here we describe two new families with novel mutations, including one with a whole gene PLS3 deletion, and review the literature on 9 previously reported cases. RESULTS: Hemizygous male carriers presented with multiple peripheral bone fractures, low bone mineral density (BMD), and vertebral compression fractures. Heterozygous female carriers did not have a history of fragility fractures, although 1 individual presented with low BMD. Apart from greyish-tinged sclera, no other extraskeletal features of osteogenesis imperfecta were identified. Histomorphometry from a transiliac bone biopsy in one of our index patients demonstrated significantly low trabecular bone volume with increased bone turnover. Bisphosphonate treatment was associated with a reduction in the fracture rate and increased bone density. CONCLUSION: Hemizygous mutations in PLS3 may cause a monogenic form of X-linked osteoporosis presenting in childhood with a nonspecific phenotype. No characteristic ocular, dental, or joint abnormalities are defined. When genetic testing is undertaken to investigate for primary causes of bone fragility, we suggest PLS3 be included in order not to miss this diagnosis.
BACKGROUND AND OBJECTIVES:Plastin 3 (PLS3) mutations are associated with an X-linked osteoporosis. Here we describe two new families with novel mutations, including one with a whole gene PLS3 deletion, and review the literature on 9 previously reported cases. RESULTS: Hemizygous male carriers presented with multiple peripheral bone fractures, low bone mineral density (BMD), and vertebral compression fractures. Heterozygous female carriers did not have a history of fragility fractures, although 1 individual presented with low BMD. Apart from greyish-tinged sclera, no other extraskeletal features of osteogenesis imperfecta were identified. Histomorphometry from a transiliac bone biopsy in one of our index patients demonstrated significantly low trabecular bone volume with increased bone turnover. Bisphosphonate treatment was associated with a reduction in the fracture rate and increased bone density. CONCLUSION: Hemizygous mutations in PLS3 may cause a monogenic form of X-linked osteoporosis presenting in childhood with a nonspecific phenotype. No characteristic ocular, dental, or joint abnormalities are defined. When genetic testing is undertaken to investigate for primary causes of bone fragility, we suggest PLS3 be included in order not to miss this diagnosis.
Authors: Christopher L Schwebach; Elena Kudryashova; Weili Zheng; Matthew Orchard; Harper Smith; Lucas A Runyan; Edward H Egelman; Dmitri S Kudryashov Journal: Bone Res Date: 2020-05-22 Impact factor: 13.567
Authors: Sanne Treurniet; Elisabeth M W Eekhoff; Felix N Schmidt; Dimitra Micha; Björn Busse; Nathalie Bravenboer Journal: Front Endocrinol (Lausanne) Date: 2020-06-23 Impact factor: 5.555
Authors: Christopher L Schwebach; Elena Kudryashova; Weili Zheng; Matthew Orchard; Harper Smith; Lucas A Runyan; Edward H Egelman; Dmitri S Kudryashov Journal: Bone Res Date: 2020-05-22 Impact factor: 13.567
Authors: Riikka E Mäkitie; Tuukka Niinimäki; Maria Suo-Palosaari; Anders Kämpe; Alice Costantini; Sanna Toiviainen-Salo; Jaakko Niinimäki; Outi Mäkitie Journal: Front Endocrinol (Lausanne) Date: 2020-06-23 Impact factor: 5.555