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Use of targeted next‐generation sequencing for molecular diagnosis of craniosynostosis: Identification of a novel de novo mutation of EFNB 1
Author(s) -
Yamamoto Toshiyuki,
Igarashi Naru,
Shimojima Keiko,
Sangu Noriko,
Sakamoto Yuko,
Shimoji Kazuaki,
Niijima Shinichi
Publication year - 2016
Publication title -
congenital anomalies
Language(s) - English
Resource type - Journals
eISSN - 1741-4520
pISSN - 0914-3505
DOI - 10.1111/cga.12123
Subject(s) - sanger sequencing , craniosynostosis , hypertelorism , medicine , genetics , crouzon syndrome , craniosynostoses , mutation , dna sequencing , gene , biology
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‐ B 1 gene ( EFNB 1 ) located in the X q13.1 region. In this study, we performed targeted, massively parallel sequencing using a next‐generation sequencer, and identified a novel EFNB 1 mutation, c.270_271del CA , 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.