Rare homozygous SERPINF1 pathogenic variant causing autosomal recessive osteogenesis imperfecta type VI in two unrelated Ecuadorian families

Background Osteogenesis imperfecta (OI) type VI is a rare autosomal recessive disorder characterized by bone fragility and defective mineralization, caused by pathogenic variants in the SERPINF1 gene. This subtype typically presents with increased fracture susceptibility and abnormal bone histology due to impaired osteoid mineralization. Case presentation We report the clinical, radiological, and molecular findings of three unrelated patients diagnosed with OI type VI, all carrying the same rare homozygous pathogenic variant SERPINF1 : c.295C > T; p.(Arg99*), which introduces a premature stop codon. All three patients experienced their first fractures after 12 months of age, predominantly affecting the femur, with an average of 10 to 15 fractures during early childhood. Severe vertebral involvement with scoliosis was observed in all cases, without neurological compromise or dentinogenesis imperfecta. The oldest patient, a 46-year-old woman, remains ambulatory. The youngest patient, a 12-year-old boy, is no longer able to walk despite bisphosphonate therapy (pamidronate). The third patient died at 21 years of age due to a respiratory complication. Conclusions This report contributes new information on a rare form of OI and highlights the recurrence of an uncommon SERPINF1 variant in apparently unrelated families. These findings expand the mutational spectrum of SERPINF1 and underscore the importance of genetic screening in understudied populations, where some variants may result from a founder effect.