Novel mutations in FKBP10 in Chinese patients with osteogenesis imperfecta and their treatment with zoledronic acid

Osteogenesis imperfecta (OI) is a group of hereditary disorders characterized by decreased bone mass and increased fracture risk. The majority of OI cases have an autosomal dominant pattern of inheritance and are usually caused by mutations in genes encoding type I collagen. OI cases of autosomal recessive inheritance are rare, and OI type XI is attributable to mutation of the FKBP10 gene. Here, we used next-generation sequencing and Sanger sequencing to detect mutations in FKBP10 and to analyze their relation to the phenotypes of OI type XI in three Chinese patients. We also evaluated the efficacy of zoledronic acid treatment in these patients. Two of the affected patients had novel compound heterozygous mutations, one patient with c. 343C>T (p.R115X) in exon 2 and c. 1085delC (p. A362fsX1) in exon 7, and the other patient with c. 879C>G (p.Y293X) in exon 5 and c. 918-3C>G in intron 5. In the third proband, we identified a homozygous single base-pair duplication, c. 831dupC (p. G278RfsX95) in exon 5. In conclusion, we report for the first time that these novel pathogenic mutations of FKBP10 can lead to the extremely rare type XI OI without contractures, which expands the genotypic spectrum of OI. The phenotypes of these patients are similar to patients with types III or IV OI, and zoledronic acid is effective in increasing BMD, inhibiting bone resorption biomarkers and reducing fractures of these patients.