مورد إلكتروني
A craniosynostosis massively parallel sequencing panel study in 309 Australian and New Zealand patients: findings and recommendations
| العنوان: | A craniosynostosis massively parallel sequencing panel study in 309 Australian and New Zealand patients: findings and recommendations |
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| المؤلفون: | Lee, E., Le, T., Zhu, Y., Elakis, G., Turner, A., Lo, W., Venselaar, H., Verrenkamp, C. -A., Snow, N., Mowat, D., Kirk, E. P., Sachdev, R., Smith, J., Brown, N. J., Wallis, M., Barnett, C., Mckenzie, F., Freckmann, M. -L., Collins, F., Chopra, M., Gregersen, N., Hayes, I., Rajagopalan, S., Tan, T. Y., Stark, Z., Savarirayan, R., Yeung, A., Ades, L., Gattas, M., Gibson, K., Gabbett, M., Amor, D. J., Lattanzi, Wanda, Boyd, S., Haan, E., Gianoutsos, M., Cox, T. C., Buckley, M. F., Roscioli, T., Lattanzi W. (ORCID:0000-0003-3092-4936) |
| بيانات النشر: | Nature Publishing Group 2018 |
| نوع الوثيقة: | Electronic Resource |
| مستخلص: | 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. |
| مصطلحات الفهرس: | coronal, craniosynostosi, EFNB1, panel, TCF12, Australia, Basic Helix-Loop-Helix Transcription Factor, Cohort Studie, Cranial Suture, Craniosynostose, DNA-Binding Protein, Ephrin-B1, Female, Fibroblast Growth Factor 10, Genetic Testing, High-Throughput Nucleotide Sequencing, Human, Male, New Zealand, Nuclear Protein, Prospective Studie, Receptor, Fibroblast Growth Factor, Type 1, Repressor Protein, Retrospective Studie, Transcription Factor, Twist-Related Protein 1, Settore BIO/13 - BIOLOGIA APPLICATA, info:eu-repo/semantics/article |
| URL: | info:eu-repo/semantics/altIdentifier/pmid/29215649 info:eu-repo/semantics/altIdentifier/wos/WOS:000445531800020 volume:20 issue:9 firstpage:1061 lastpage:1068 numberofpages:8 issueyear:2018 journal:GENETICS IN MEDICINE |
| الإتاحة: | Open access content. Open access content |
| ملاحظة: | English |
| أرقام أخرى: | SYC oai:publicatt.unicatt.it:10807/152979 10.1038/gim.2017.214 info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85053737381 1196083687 |
| المصدر المساهم: | UNIV CATTOLICA DEL SACRO CUORE From OAIster®, provided by the OCLC Cooperative. |
| رقم الأكسشن: | edsoai.on1196083687 |
| قاعدة البيانات: | OAIster |
| الوصف غير متاح. |