Durkin, A., DeVile, C., Arundel, P. et al. (11 more authors) (2021) Expanding the phenotype of SPARC-related osteogenesis imperfecta : clinical findings in two patients with pathogenic variants in SPARC and literature review. Journal of Medical Genetics, 59 (8). pp. 810-816. ISSN 0022-2593
Abstract
Background: Secreted protein, acidic, cysteine rich (SPARC)-related osteogenesis imperfecta (OI), also referred to as OI type XVII, was first described in 2015, since then there has been only one further report of this form of OI. SPARC is located on chromosome 5 between bands q31 and q33. The encoded protein is necessary for calcification of the collagen in bone, synthesis of extracellular matrix and the promotion of changes to cell shape.
Methods: We describe a further two patients with previously unreported homozygous SPARC variants with OI: one splice site; one nonsense pathogenic variant. We present detailed information on the clinical and radiological phenotype and correlate this with their genotype. There are only two previous reports by Mendozo-Londono et al and Hayat et al with clinical descriptions of patients with SPARC variants.
Results: From the data we have obtained, common clinical features in individuals with OI type XVII caused by SPARC variants include scoliosis (5/5), vertebral compression fractures (5/5), multiple long bone fractures (5/5) and delayed motor development (3/3). Interestingly, 2/4 patients also had abnormal brain MRI, including high subcortical white matter changes, abnormal fluid-attenuated inversion in the para-atrial white matter and a large spinal canal from T10 to L1. Of significance, both patients reported here presented with significant neuromuscular weakness prompting early workup.
Conclusion: Common phenotypic expressions include delayed motor development with neuromuscular weakness, scoliosis and multiple fractures. The data presented here broaden the phenotypic spectrum establishing similar patterns of neuromuscular presentation with a presumed diagnosis of ‘myopathy’.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2021 Author(s) (or their employer(s)). This is an author-produced version of a paper subsequently published in Journal of Medical Genetics. Available under the CC BY-NC license (https://creativecommons.org/licenses/by-nc/4.0/). |
Keywords: | SPARC; Osteogenesis Imperfecta; scoliosis; myopathy |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Sheffield Teaching Hospitals |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 19 Jan 2022 14:50 |
Last Modified: | 25 Jun 2024 07:48 |
Status: | Published |
Publisher: | BMJ Publishing Group |
Refereed: | Yes |
Identification Number: | 10.1136/jmedgenet-2021-107942 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:182719 |
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Filename: Durkin et al, 2021. Expanding the phenotype of SPARC-related osteogenesis imperfecta.pdf
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