Secreted protein, acidic, cysteine-rich (SPARC) is a glycoprotein that binds to collagen type I
and other proteins in the extracellular matrix. Using whole-exome sequencing to identify the
molecular defect in two unrelated girls with severe bone fragility and a clinical diagnosis of
osteogenesis imperfecta type IV, we identified two homozygous variants in SPARC
(GenBank: NM_003118. 3; c. 497G> A [p. Arg166His] in individual 1; c. 787G> A [p.
Glu263Lys] in individual 2). Published modeling and site-directed mutagenesis studies had …

Objectives: We sought to identify the disease-causing mutations in two unrelated girls with a
clinical diagnosis of osteogenesis imperfecta type IV. Methods: Whole-exome sequencing
and cellular studies in skin fibroblasts were conducted. Results: We identified two
homozygous variants in SPARC (NM_003118. 3; c. 497G> A (p. Arg166His) in individual 1;
c. 787G> A (p. Glu263Lys) in individual 2). Secreted protein, acidic, cysteine-rich (SPARC) is
a glycoprotein that binds to collagen type I and other proteins in the extracellular matrix …