TY - JOUR T1 - Expanding the phenotype of <em>SPARC</em>-related osteogenesis imperfecta: clinical findings in two patients with pathogenic variants in <em>SPARC</em> and literature review JF - Journal of Medical Genetics JO - J Med Genet DO - 10.1136/jmedgenet-2021-107942 SP - jmedgenet-2021-107942 AU - Anna Durkin AU - Catherine DeVile AU - Paul Arundel AU - Mary Bull AU - Jennifer Walsh AU - Nicholas J Bishop AU - Emilie Hupin AU - Susan Parekh AU - Ramesh Nadarajah AU - Amaka C Offiah AU - Alistair Calder AU - Joanna Brock AU - Duncan Baker AU - Meena Balasubramanian Y1 - 2021/08/29 UR - http://jmg.bmj.com/content/early/2021/08/29/jmedgenet-2021-107942.abstract N2 - 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’.All data relevant to the study are included in the article or uploaded as supplemental information. ER -