Abstract

Osteogenesis imperfecta (OI) is a genetically and phenotypically heterogeneous group of disorders primarily characterized by bone fragility, impaired growth, and skeletal deformities. Although OI was historically attributed to monoallelic pathogenic variants in COL1A1 and COL1A2, recent advances have identified autosomal recessive forms caused by defects in genes involved in collagen biosynthesis and processing. SERPINH1 encodes heat shock protein 47 (HSP47), a collagen-specific molecular chaperone essential for proper folding of the procollagen triple helix and its transport to the Golgi apparatus. Loss-of-function variants in SERPINH1 cause OI type X, a rare autosomal recessive form associated with moderate to severe bone fragility. We evaluated two Turkish siblings with clinical features of OI, including short stature, recurrent fractures, low bone mineral density, and skeletal deformities. Exome sequencing identified a novel homozygous missense variant in SERPINH1 (NM_001235.5: c.250G>C; p.G84R) in both siblings. Despite sharing the same genotype, they exhibited marked intrafamilial phenotypic variability: the 8-year-old brother presented with early-onset, severe skeletal manifestations, whereas his 11-year-old sister showed a milder, later-onset phenotype.

This report expands the genotypic and phenotypic spectrum of SERPINH1-related OI, highlights intrafamilial variability, and adds further data on Turkish patients with this rare condition.