Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/118309
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Type: Journal article
Title: A craniosynostosis massively parallel sequencing panel study in 309 Australian and New Zealand patients: findings and recommendations
Author: Lee, E.
Le, T.
Zhu, Y.
Elakis, G.
Turner, A.
Lo, W.
Venselaar, H.
Verrenkamp, C.
Snow, N.
Mowat, D.
Kirk, E.
Sachdev, R.
Smith, J.
Brown, N.
Wallis, M.
Barnett, C.
McKenzie, F.
Freckmann, M.
Collins, F.
Chopra, M.
et al.
Citation: Genetics in Medicine, 2018; 20(9):1061-1068
Publisher: Springer Nature
Issue Date: 2018
ISSN: 1098-3600
1530-0366
Statement of
Responsibility: 
Eric Lee … Chris Barnett … Eric Haan … et al.
Abstract: Purpose: The craniosynostoses are characterized by premature fusion of one or more cranial sutures. The relative contribution of previously reported genes to craniosynostosis in large cohorts is unclear. Here we report on the use of a massively parallel sequencing panel in individuals with craniosynostosis without a prior molecular diagnosis. Methods: A 20-gene panel was designed based on the genes' association with craniosynostosis, and clinically validated through retrospective testing of an Australian and New Zealand cohort of 233 individuals with craniosynostosis in whom previous testing had not identified a causative variant within FGFR1-3 hot-spot regions or the TWIST1 gene. An additional 76 individuals were tested prospectively. Results: Pathogenic or likely pathogenic variants in non-FGFR genes were identified in 43 individuals, with diagnostic yields of 14% and 15% in retrospective and prospective cohorts, respectively. Variants were identified most frequently in TCF12 (N = 22) and EFNB1 (N = 8), typically in individuals with nonsyndromic coronal craniosynostosis or TWIST1-negative clinically suspected Saethre-Chotzen syndrome. Clinically significant variants were also identified in ALX4, EFNA4, ERF, and FGF10. Conclusion: These findings support the clinical utility of a massively parallel sequencing panel for craniosynostosis. TCF12 and EFNB1 should be included in genetic testing for nonsyndromic coronal craniosynostosis or clinically suspected Saethre-Chotzen syndrome.
Keywords: Coronal; craniosynostosis; EFNB1; panel; TCF12
Rights: © American College of Medical Genetics and Genomics
RMID: 0030079346
DOI: 10.1038/gim.2017.214
Appears in Collections:Medicine publications

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