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Novel pathogenic variants in SPARC as cause of osteogenesis imperfecta: Two case reports
Journal article   Open access   Peer reviewed

Novel pathogenic variants in SPARC as cause of osteogenesis imperfecta: Two case reports

Silvia Storoni, Luca Celli, Lidiia Zhytnik, Katre Maasalu, Aare Märtson, Sulev Kõks, Sergey Khmyzov, Andrei Pashenko, Alessandra Maugeri, Anna Zambrano, …
European Journal of Medical Genetics, Vol.66(11), 104857
2023
DOI: https://doi.org/10.1016/j.ejmg.2023.104857
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CC BY V4.0,  Open Access

Abstract

Osteogenesis imperfecta SPARC gene Pathogenic variants Clinical phenotype Bisphosphonates
Pathogenic variants in SPARC cause a rare autosomal recessive form of osteogenesis imperfecta (OI), classified as OI type XVII, which was first reported in 2015. Only six patient cases with this specific form of OI have been reported to date. The SPARC protein plays a crucial role in the calcification of collagen in bone, synthesis of the extracellular matrix, and the regulation of cell shape. In this case report, we describe the phenotype of two patients with SPARC-related OI, including a patient with two novel pathogenic variants in the SPARC gene. Targeted Next Generation Sequencing revealed new compound heterozygous variants (c.484G > A p.(Glu162Lys)) and c.496C > T p.(Arg166Cys)) in one patient and a homozygous nonsense pathogenic variant (c.145C > T p.(Gln49*)) in the other. In line with previously reported cases, the two OI patients presented delayed motor development, muscular weakness, scoliosis, and multiple fractures. Interestingly, our study reports for the first time the occurrence of dentinogenesis imperfecta. The study also reports the effectiveness of bisphosphonate treatment for OI type XVII. This article enhances the genetic, clinical, therapeutic, and radiological understanding of SPARC-related OI.

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