title: Novel mutations in FKBP10 in Chinese patients with osteogenesis imperfecta and their treatment with zoledronic acid.
abstract: 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.
authors.affiliation: Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Xiao-Jie
authors.initials: XJ
authors.lastname: Xu
authors.affiliation: Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Lv
authors.affiliation: Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Jian-Yi
authors.initials: JY
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Dou-Dou
authors.initials: DD
authors.lastname: Ma
authors.affiliation: Research and Development Center, Binhai Genomics Institute, Tianjin, China.|Research and Development Center, Tianjin Translational Genomics Center, Tianjin, China.
authors.lastname: Asan
authors.affiliation: Research and Development Center, Binhai Genomics Institute, Tianjin, China.|Research and Development Center, Tianjin Translational Genomics Center, Tianjin, China.
authors.forename: Jia-Wei
authors.initials: JW
authors.lastname: Wang
authors.affiliation: Research and Development Center, Binhai Genomics Institute, Tianjin, China.|Research and Development Center, Tianjin Translational Genomics Center, Tianjin, China.
authors.forename: Li-Jie
authors.initials: LJ
authors.lastname: Song
authors.affiliation: Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Ou
authors.initials: O
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Wei-Bo
authors.initials: WB
authors.lastname: Xia
authors.affiliation: Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Xing
authors.affiliation: Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Li
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D015519:Bone Density / Q000187:drug effects / Q000235:genetics; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001862:Bone Resorption / Q000517:prevention & control; D002648:Child; D002675:Child, Preschool; D002681:China / Q000453:epidemiology; D024042:Collagen Type I / Q000235:genetics; D000090602:Collagen Type I, alpha 1 Chain; D004164:Diphosphonates / Q000627:therapeutic use*; D005260:Female; D050723:Fractures, Bone / Q000188:drug therapy / Q000453:epidemiology / Q000517:prevention & control*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D010013:Osteogenesis Imperfecta / Q000188:drug therapy* / Q000235:genetics*; D017422:Sequence Analysis, DNA; D022021:Tacrolimus Binding Proteins / Q000235:genetics*; D055815:Young Adult; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; C000601279:COL1A2 protein, human; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D004164:Diphosphonates; C575746:IFITM5 protein, human; D007093:Imidazoles; D008565:Membrane Proteins; D000077211:Zoledronic Acid; D022021:Tacrolimus Binding Proteins; C110054:FKBP10 protein, human