Novel Mutations in PLOD2 Cause Rare Bruck Syndrome

AbstractBruck syndrome is a rare autosomal recessive form of osteogenesis imperfecta (OI), which is mainly characterized by joint contractures and recurrent fragility fractures. Mutations inFKBP10 andPLOD2 were identified as the underlying genetic defects of Bruck syndrome. Here we investigated the phenotypes and the pathogenic mutations of three unrelated Chinese patients with Bruck syndrome. Clinical fractures, bone mineral density (BMD), bone turnover biomarkers, and skeletal images were evaluated in detail. The pathogenic mutations were identified by targeted next-generation sequencing and subsequently confirmed by Sanger sequencing and cosegregation analysis. We also evaluated the effects of zoledronic acid on bone fracture incidence and BMD of the patients. Three patients had congenital joint contractures, recurrent fragility fractures, camptodactyly, clubfoot, scoliosis, but without dentinogenesis imperfecta and hearing loss. Five novel heterozygous mutations were detected inPLOD2, including three heterozygous missense mutations (c.1138C>T, p.Arg380Cys; c.1153T>C, p.Cys385Arg; and c.1982G>A, p.Gly661Asp), one heterozygous nonsense mutation (c.2038C>T, p.Arg680X), and one heterozygous splice-site mutation (c.503-2A>G). Their parents were all heterozygous carriers of these mutations inPLOD2. No clear genotype –phenotype correlations were found in these patients withPLOD2 mutations. Z-score of BMD was significantly increased, but scoliosis progressed and ...
Source: Calcified Tissue International - Category: Orthopaedics Source Type: research