title: Use of targeted next-generation sequencing for molecular diagnosis of craniosynostosis: Identification of a novel de novo mutation of EFNB1.
abstract: Craniofrontonasal syndrome (CFNS; MIM#304110) is characterized by asymmetric facial features with hypertelorism and a broad bifid nose due to synostosis of the coronal suture. CFNS shows a unique X-linked inheritance pattern (most affected patients are female and obligate male carriers exhibit a mild manifestation or no typical features at all) associated with the ephrin-B1 gene (EFNB1) located in the Xq13.1 region. In this study, we performed targeted, massively parallel sequencing using a next-generation sequencer, and identified a novel EFNB1 mutation, c.270_271delCA, in a Japanese female patient with craniosynostosis. Because subsequent Sanger sequencing identified no mutation in either parent, this mutation was determined to be de novo in origin. After obtaining molecular diagnosis, a retrospective clinical evaluation confirmed the clinical diagnosis of CFNS in this patient. Comprehensive molecular diagnosis using a next-generation sequencer would be beneficial for early diagnosis of the patients with undiagnosed craniosynostosis.
authors.affiliation: Tokyo Women's Medical University Institute for Integrated Medical Sciences, Tokyo, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Department of Pediatrics, Juntendo University Nerima Hospital, Tokyo, Japan.
authors.forename: Naru
authors.initials: N
authors.lastname: Igarashi
authors.affiliation: Tokyo Women's Medical University Institute for Integrated Medical Sciences, Tokyo, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Shimojima
authors.affiliation: Tokyo Women's Medical University Institute for Integrated Medical Sciences, Tokyo, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Sangu
authors.affiliation: Department of Orthopedics, Juntendo University Nerima Hospital, Tokyo, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Sakamoto
authors.affiliation: Department of Neurosurgery, Juntendo University, Tokyo, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Shimoji
authors.affiliation: Department of Pediatrics, Juntendo University Nerima Hospital, Tokyo, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Niijima
mesh_terms: D003398:Craniosynostoses / Q000175:diagnosis* / Q000235:genetics*; D004252:DNA Mutational Analysis; D036387:Ephrin-B1 / Q000235:genetics*; D005260:Female; D056973:Four-Dimensional Computed Tomography; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D009154:Mutation; D017384:Sequence Deletion
chemical_list: C484288:EFNB1 protein, human; D036387:Ephrin-B1
keywords: craniofrontonasal syndrome; craniosynostosis; ephrin-B1; massively parallel sequencing; mutation; next-generation sequencer