Article Text

other Versions

Download PDFPDF
Original research
Expanding the phenotype of SPARC-related osteogenesis imperfecta: clinical findings in two patients with pathogenic variants in SPARC and literature review
  1. Anna Durkin1,
  2. Catherine DeVile2,
  3. Paul Arundel3,
  4. Mary Bull4,
  5. Jennifer Walsh4,5,
  6. Nicholas J Bishop3,5,
  7. Emilie Hupin2,
  8. Susan Parekh6,
  9. Ramesh Nadarajah2,
  10. Amaka C Offiah3,5,
  11. Alistair Calder7,
  12. Joanna Brock8,
  13. Duncan Baker8,
  14. Meena Balasubramanian3,5,9
  1. 1The University of Sheffield Medical School, Sheffield, UK
  2. 2Highly Specialised OI Service, Great Ormond Street Hospital For Children NHS Foundation Trust, London, UK
  3. 3Highly Specialised OI Service, Sheffield Children's NHS Foundation Trust, Sheffield, UK
  4. 4Metabolic Bone Centre, Northern General Hospital, Sheffield, UK
  5. 5Department of Oncology & Metabolism, The University of Sheffield, Sheffield, UK
  6. 6Eastman Dental Institute, University College London, London, UK
  7. 7Radiology Department, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK
  8. 8Connective Tissue Disorders Service, Sheffield Diagnostic Genetics Service, Sheffield Children's Hospital, Sheffield, UK
  9. 9Sheffield Clinical Genetics Service, Sheffield Children's NHS Foundation Trust, Sheffield, UK
  1. Correspondence to Dr Meena Balasubramanian, Sheffield Clinical Genetics Service, Sheffield Children's NHS Foundation Trust, Sheffield S10 2TH, UK; meena.balasubramanian{at}


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’.

  • genetics
  • fractures
  • bone

Data availability statement

All data relevant to the study are included in the article or uploaded as supplemental information.

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Data availability statement

All data relevant to the study are included in the article or uploaded as supplemental information.

View Full Text


  • Twitter @MeenaBalasubra5

  • Contributors AD collated phenotype data. All authors contributed to clinical, genetic and radiology data collection for both patients, write-up and approved final manuscript. MB supervised the project.

  • Funding MB’s research is funded by the MRC (MR/V037307/1); no specific funding obtained for this specific study.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.