title: Molecular genetic analysis of TWIST1 and FGFR3 genes in Korean patients with coronal synostosis: identification of three novel TWIST1 mutations.
abstract: BACKGROUND
  Craniosynostosis is very heterogeneous in terms of its causes, presentation, and management. In particular, coronal synostosis evidences a higher tendency to be genetically caused, and TWIST1 and FGFR3 have been identified as major causative genes. The authors analyzed the clinical and molecular characteristics of Korean patients with coronal synostosis in this study.
  
  
  METHODS
  Forty-three Korean patients with unicoronal or bicoronal synostosis were included in this study. All samples were first screened for TWIST1 and FGFR3 mutation hot spots, and the negative samples were subsequently screened for FGFR2. The patients' clinical features were analyzed and compared.
  
  
  RESULTS
  Seven sequence alterations (six in TWIST1 and one in FGFR3) were identified in 11 patients (25.6 percent). Three novel TWIST1 mutations were detected, and p.P250R was the only mutation in FGFR3. Bicoronal cases evidenced a much higher mutation detection rate (52.9 percent) than unicoronal cases (7.7 percent). In the TWIST1 group, five patients had Saethre-Chotzen syndrome, and one was nonsyndromic. In the FGFR3 group, four patients had Muenke syndrome, and one was nonsyndromic. The majority of associated anomalies, with the exception of psychomotor retardation and Chiari malformation, were detected more frequently in TWIST1 patients than in FGFR3 p.P250R patients.
  
  
  CONCLUSIONS
  This study is, to the best of the authors' knowledge, the first to illustrate the frequency and spectrum of mutations in TWIST1 and FGFR3 in Korea. Considering that molecular diagnosis techniques can prove helpful in providing adequate genetic counseling and guidance, genetic screening for TWIST1 and FGFR3 p.P250R in cases of coronal synostosis is recommended.
authors.affiliation: Seoul and Suwon, Korea From the Department of Pediatrics, Seoul National University College of Medicine; the Departments of Medical Genetics, Plastic and Reconstructive Surgery, and Neurosurgery, Ajou University School of Medicine; and the Genetic Clinic and Laboratory, Ajou University Hospital.
authors.forename: Jung Min
authors.initials: JM
authors.lastname: Ko
authors.forename: Seon-Yong
authors.initials: SY
authors.lastname: Jeong
authors.forename: Jung-Ah
authors.initials: JA
authors.lastname: Yang
authors.forename: Dong Ha
authors.initials: DH
authors.lastname: Park
authors.forename: Soo Han
authors.initials: SH
authors.lastname: Yoon
mesh_terms: D000168:Acrocephalosyndactylia / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D003398:Craniosynostoses / Q000235:genetics*; D005260:Female; D005820:Genetic Testing; D006801:Humans; D007223:Infant; D007723:Korea; D008297:Male; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D051497:Receptor, Fibroblast Growth Factor, Type 2; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics*; D051879:Twist-Related Protein 1 / Q000235:genetics*
chemical_list: D009687:Nuclear Proteins; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1; C496353:FGFR2 protein, human; C496365:FGFR3 protein, human; D051497:Receptor, Fibroblast Growth Factor, Type 2; D051498:Receptor, Fibroblast Growth Factor, Type 3