title: A novel RUNX2 missense mutation predicted to disrupt DNA binding causes cleidocranial dysplasia in a large Chinese family with hyperplastic nails.
abstract: BACKGROUND
  Cleidocranial dysplasia (CCD) is a dominantly inherited disease characterized by hypoplastic or absent clavicles, large fontanels, dental dysplasia, and delayed skeletal development. The purpose of this study is to investigate the genetic basis of Chinese family with CCD.
  
  
  METHODS
  Here, a large Chinese family with CCD and hyperplastic nails was recruited. The clinical features displayed a significant intrafamilial variation. We sequenced the coding region of the RUNX2 gene for the mutation and phenotype analysis.
  
  
  RESULTS
  The family carries a c.T407C (p.L136P) mutation in the DNA- and CBFbeta-binding Runt domain of RUNX2. Based on the crystal structure, we predict this novel missense mutation is likely to disrupt DNA binding by RUNX2, and at least locally affect the Runt domain structure.
  
  
  CONCLUSIONS
  A novel missense mutation was identified in a large Chinese family with CCD with hyperplastic nails. This report further extends the mutation spectrum and clinical features of CCD. The identification of this mutation will facilitate prenatal diagnosis and preimplantation genetic diagnosis.
authors.affiliation: The prenatal diagnostic Center of Wenzhou City, Department of genetics of Wenzhou No2 Hospital, Wenzhou, China. tsh006@163.com
authors.forename: Shaohua
authors.initials: S
authors.lastname: Tang
authors.forename: Qiyu
authors.initials: Q
authors.lastname: Xu
authors.forename: Xueqin
authors.initials: X
authors.lastname: Xu
authors.forename: Jicheng
authors.initials: J
authors.lastname: Du
authors.forename: Xuemei
authors.initials: X
authors.lastname: Yang
authors.forename: Yusheng
authors.initials: Y
authors.lastname: Jiang
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Wang
authors.forename: Nancy
authors.initials: N
authors.lastname: Speck
authors.forename: Taosheng
authors.initials: T
authors.lastname: Huang
mesh_terms: D000328:Adult; D002681:China; D002973:Cleidocranial Dysplasia / Q000235:genetics*; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D006965:Hyperplasia; D008297:Male; D020125:Mutation, Missense; D009264:Nails, Malformed / Q000235:genetics* / Q000473:pathology; D010375:Pedigree
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D004268:DNA-Binding Proteins; C493709:RUNX2 protein, human