A case of osteogenesis imperfecta Sillence type III with a novel pathogenic variant in the P3H1 gene

Abstract

 Osteogenesis imperfecta（OI）is a skeletal disorder characterized by generalized bone fragility and a predisposition to fracture. The patient was a female infant suspected of having a skeletal disorder owing to limb deformities detected in utero. She was delivered by cesarean section at 38 weeks and 5 days of gestation with a birth weight of 2,322 g and mild respiratory distress. Genetic testing performed after birth identified pathogenic variants in the P3H1 gene, leading to a diagnosis of OI Type VIII according to the Online Mendelian Inheritance in Man classification. The identified pathogenic variants were c.484delG（p.Ala162LeufsTer22）and c.1453G ＞ T（p.Glu485Ter）, the latter of which is a novel variant that has not been reported previously. On day 40 after birth, intravenous disodium pamidronate hydrate was administered. Despite treatment, the infant experienced multiple limb fractures that began at 8 months of age. Additional findings included blue sclerae and dentinogenesis imperfecta in the primary teeth. On the basis of these clinical features, the patient was diagnosed with Sillence Type III. OI caused by P3H1 pathogenic variants is rare, with the present case being the second reported in Japan. Further accumulation of data on genotype-phenotype correlations in P3H1-related OI is essential for a better understanding of this condition.