A novel mutation in PLS3 causes extremely rare X‐linked osteogenesis imperfecta

BACKGROUND: Osteogenesis imperfecta (OI) is a phenotypically and genetically heterogeneous bone disease characterized by bone fragility and recurrent fractures. X‐linked inherited OI with mutation in PLS3 is so rare that its genotype–phenotype characteristics are not available. METHODS: We designed a novel targeted next‐generation sequencing (NGS) panel with the candidate genes of OI to detect pathogenic mutations and confirmed them by Sanger sequencing. The phenotypes of the patients were also investigated. RESULTS: The proband, a 12‐year‐old boy from a nonconsanguineous family, experienced multiple fractures of long bones and vertebrae and had low bone mineral density (BMD Z‐score of −3.2 to −2.0). His younger brother also had extremity fractures. A novel frameshift mutation (c.1106_1107insGAAA; p.Phe369Leufs*5) in exon 10 of PLS3 was identified in the two patients, which was inherited from their mother who had normal BMD. Blue sclerae were the only extraskeletal symptom in all affected individuals. Zoledronic acid was beneficial for increasing BMD and reshaping the compressed vertebral bodies of the proband. CONCLUSION: We first identify a novel mutation in PLS3 that led to rare X‐linked OI and provide practical information for the diagnosis and treatment of this disease.