TY - JOUR
T1 - Novel pathogenic variants in SPARC as cause of osteogenesis imperfecta
T2 - Two case reports
AU - Storoni, Silvia
AU - Celli, Luca
AU - Zhytnik, Lidiia
AU - Maasalu, Katre
AU - Märtson, Aare
AU - Kõks, Sulev
AU - Khmyzov, Sergey
AU - Pashenko, Andrei
AU - Maugeri, Alessandra
AU - Zambrano, Anna
AU - Celli, Mauro
AU - Eekhoff, Elisabeth M. W.
AU - Micha, Dimitra
N1 - Funding Information: All authors were involved in study conception/design, data analysis and/or interpretation and in writing/critical review of draft versions of this manuscript. All authors approved the final version for submission and publication. This publication has been supported by ERN BOND - European Reference Network for rare BONeDiseases, which is partly co-funded by the European Union within the framework of the EU4Health Programme 2021–2027." Publisher Copyright: © 2023
PY - 2023/11/1
Y1 - 2023/11/1
N2 - 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.
AB - 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.
KW - Bisphosphonates
KW - Clinical phenotype
KW - Osteogenesis imperfecta
KW - Pathogenic variants
KW - SPARC gene
UR - http://www.scopus.com/inward/record.url?scp=85172463731&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.ejmg.2023.104857
DO - https://doi.org/10.1016/j.ejmg.2023.104857
M3 - Article
C2 - 37758164
SN - 1769-7212
VL - 66
JO - European journal of medical genetics
JF - European journal of medical genetics
IS - 11
M1 - 104857
ER -