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

Area of Science:

• Genetics and Molecular Biology
• Pediatric Endocrinology
• Orthopedics

Background:

• Osteogenesis Imperfecta (OI) type XVII is a rare autosomal recessive disorder caused by pathogenic variants in the SPARC gene.
• The SPARC protein is vital for bone calcification, extracellular matrix synthesis, and cell shape regulation.
• Only six cases of SPARC-related OI have been previously reported worldwide.

Observation:

• This case report describes two pediatric patients diagnosed with SPARC-related OI.
• Genetic analysis identified compound heterozygous novel variants (c.484G>A p.(Glu162Lys) and c.496C>T p.(Arg166Cys)) in one patient and a homozygous nonsense variant (c.145C>T p.(Gln49*)) in the other.
• Clinical presentation included delayed motor development, muscle weakness, scoliosis, and multiple fractures, consistent with previous reports.

Findings:

• This study reports dentinogenesis imperfecta as a novel clinical manifestation of SPARC-related OI.
• Bisphosphonate therapy demonstrated effectiveness in managing OI type XVII in the described patients.
• The genetic and clinical spectrum of SPARC-related OI is expanded with the identification of new pathogenic variants.

Implications:

• This research deepens the understanding of the genetic basis and clinical heterogeneity of SPARC-related OI.
• The findings support bisphosphonate treatment as a viable therapeutic option for OI type XVII.
• This study contributes valuable insights into the diagnosis, management, and radiological features of this rare bone fragility disorder.