title: Novel mutations in the SEC24D gene in Chinese families with autosomal recessive osteogenesis imperfecta.
abstract: We sought to characterize the phenotypes and identify the SEC24D gene mutations associated with Chinese families of osteogenesis imperfecta (OI). Using whole-exome sequencing, we discovered two novel compound SEC24D mutations of OI patients. Our study extended both the phenotypic and the genotype of the OI patients with SEC24D mutations.
  
  
  
  To date, only three compound heterozygous mutations in the SEC24D gene have been found to cause recessively inherited forms of OI. We sought to characterize the phenotypes and to identify the SEC24D gene mutations associated with Chinese families with OI.
  
  
  
  Using whole-exome sequencing in two probands, we identified two novel compound heterozygous mutations in SEC24D. In family 1, the proband was a 23-year-old male; he had recurrent fractures and dentinogenesis imperfecta. His anterior fontanel was not closed, and he showed facial dysmorphism. A computed tomography three-dimensional imaging of the cranium showed skull deformities associated with a broad ossification defect in the frontoapical area, a widened sagittal suture, and Wormian bones. In family 2, the proband was a 7-year-old boy, who also had recurrent fractures and dentinogenesis imperfecta. His anterior fontanel was not closed, and he did not have obvious facial dysmorphism.
  
  
  
  We identified one novel compound heterozygous missense substitution in the proband in family 1, including c.2723G>A (p. Cys908Tyr) and c.2842T>C (p. Ser948Pro). In the proband in family 2, we identified another novel compound heterozygous missense substitution, including c.938G>A (p. Arg313His) and c.875C>T (p. Pro292Leu).
  
  
  
  We discovered two novel compound SEC24D mutations of autosomal recessive OI patients. Our study extended both the phenotypic and the genotypic spectrum of the autosomal recessive OI patients with SEC24D mutations.
authors.affiliation: Department of Osteoporosis and Bone Diseases, Metabolic Bone Diseases and Genetic Research Unit, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China.
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Osteoporosis and Bone Diseases, Metabolic Bone Diseases and Genetic Research Unit, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China.
authors.forename: H
authors.initials: H
authors.lastname: Yue
authors.affiliation: Department of Osteoporosis and Bone Diseases, Metabolic Bone Diseases and Genetic Research Unit, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China.
authors.forename: C
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Osteoporosis and Bone Diseases, Metabolic Bone Diseases and Genetic Research Unit, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China.
authors.forename: J
authors.initials: J
authors.lastname: Gu
authors.affiliation: Department of Osteoporosis and Bone Diseases, Metabolic Bone Diseases and Genetic Research Unit, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China.
authors.forename: J
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Osteoporosis and Bone Diseases, Metabolic Bone Diseases and Genetic Research Unit, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China.
authors.forename: W
authors.initials: W
authors.lastname: Fu
authors.affiliation: Department of Osteoporosis and Bone Diseases, Metabolic Bone Diseases and Genetic Research Unit, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China.
authors.forename: W
authors.initials: W
authors.lastname: Hu
authors.affiliation: Department of Osteoporosis and Bone Diseases, Metabolic Bone Diseases and Genetic Research Unit, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China. zzl2002@medmail.com.cn.
authors.forename: Z
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D015519:Bone Density / Q000235:genetics; D016022:Case-Control Studies; D002648:Child; D004252:DNA Mutational Analysis / Q000379:methods; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D010013:Osteogenesis Imperfecta / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology; D014057:Tomography, X-Ray Computed; D033921:Vesicular Transport Proteins / Q000235:genetics*; D000073359:Exome Sequencing / Q000379:methods; D055815:Young Adult
chemical_list: C530641:SEC24D protein, human; D033921:Vesicular Transport Proteins
keywords: Chinese patients; Mutation; Osteogenesis imperfecta; SEC24D gene