Dermal fibroblast transcriptome indicates contribution of WNT signaling pathways in the pathogenesis of Apert syndrome
Cranial sutures are unossified connective tissue structures between the cranial bones, which allow expansion of these bones during development. Premature ossification of these structures is called craniosynostosis. Apert syndrome is a well-defined genetic syndrome, which is characterized by cranios...
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| Format: | Article |
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Hacettepe University Institute of Child Health
2017-12-01
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| Series: | The Turkish Journal of Pediatrics |
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| Online Access: | https://turkjpediatr.org/article/view/1043 |
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| author | Arda Çetinkaya Ekim Taşkıran Tutku Soyer Pelin Özlem Şimşek-Kiper Gülen Eda Utine Gökhan Tunçbilek Koray Boduroğlu Mehmet Alikaşifoğlu |
| author_facet | Arda Çetinkaya Ekim Taşkıran Tutku Soyer Pelin Özlem Şimşek-Kiper Gülen Eda Utine Gökhan Tunçbilek Koray Boduroğlu Mehmet Alikaşifoğlu |
| author_sort | Arda Çetinkaya |
| collection | DOAJ |
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Cranial sutures are unossified connective tissue structures between the cranial bones, which allow expansion of these bones during development. Premature ossification of these structures is called craniosynostosis. Apert syndrome is a well-defined genetic syndrome, which is characterized by craniosynostosis and arises as a result of two missense mutations in Fibroblast Growth Factor Receptor, type 2 gene (FGFR2). In this study, differentially expressed genes in dermal fibroblasts from individuals with Apert syndrome and controls were investigated to identify important pathways in the pathogenesis of Apert syndrome. For this purpose, primary skin fibroblast cultures obtained from 3 individuals with Apert syndrome and 3 controls without craniosynostosis were compared by transcriptome microarray, GeneChip Human Genome U133 Plus 2.0. As a result, 181 genes were shown to be differentially expressed between experimental groups. Among these, 10 genes, which significantly differ in Apert syndrome fibroblasts compared to controls, were shown to be involved in a common interaction network and have common Gene ontology (GO) biological processes terms. COL11A1, COMP, CPXM2, ITGA8, MGF and TNC are differentially expressed genes that have GO terms associated with extracellular matrix (ECM) organization, while FRZB, SFRP2 and WNT2 are involved in WNT signaling pathway. Reorganization of ECM and changes in WNT signaling pathway show that Apert syndrome primary fibroblast cultures may have an increased potential for bone differentiation. The results of this study support craniosynostosis in Apert syndrome may be the result of fast and early differentiation of connective tissue along the sutures.
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| format | Article |
| id | doaj-art-41f64cd4292345cab03f143d8d1cdb3c |
| institution | OA Journals |
| issn | 0041-4301 2791-6421 |
| language | English |
| publishDate | 2017-12-01 |
| publisher | Hacettepe University Institute of Child Health |
| record_format | Article |
| series | The Turkish Journal of Pediatrics |
| spelling | doaj-art-41f64cd4292345cab03f143d8d1cdb3c2025-08-20T02:01:55ZengHacettepe University Institute of Child HealthThe Turkish Journal of Pediatrics0041-43012791-64212017-12-0159610.24953/turkjped.2017.06.001Dermal fibroblast transcriptome indicates contribution of WNT signaling pathways in the pathogenesis of Apert syndromeArda ÇetinkayaEkim Taşkıran0Tutku Soyer1Pelin Özlem Şimşek-Kiper2Gülen Eda Utine3Gökhan Tunçbilek4Koray Boduroğlu5Mehmet Alikaşifoğlu6Department of Medical Genetics, Faculty of Medicine, Hacettepe University, Ankara, Turkey.Department of Pediatric Surgery, aculty of Medicine, Hacettepe University, Ankara, Turkey.Department of Pediatric Genetics, Faculty of Medicine, Hacettepe University, Ankara, Turkey.Department of Pediatric Genetics, Faculty of Medicine, Hacettepe University, Ankara, Turkey.Department of Plastic Reconstructive and Aesthetic Surgery, Faculty of Medicine, Hacettepe University, Ankara, Turkey.Department of Pediatric Genetics, Faculty of Medicine, Hacettepe University, Ankara, Turkey.Department of Medical Genetics, Faculty of Medicine, Hacettepe University, Ankara, Turkey. Cranial sutures are unossified connective tissue structures between the cranial bones, which allow expansion of these bones during development. Premature ossification of these structures is called craniosynostosis. Apert syndrome is a well-defined genetic syndrome, which is characterized by craniosynostosis and arises as a result of two missense mutations in Fibroblast Growth Factor Receptor, type 2 gene (FGFR2). In this study, differentially expressed genes in dermal fibroblasts from individuals with Apert syndrome and controls were investigated to identify important pathways in the pathogenesis of Apert syndrome. For this purpose, primary skin fibroblast cultures obtained from 3 individuals with Apert syndrome and 3 controls without craniosynostosis were compared by transcriptome microarray, GeneChip Human Genome U133 Plus 2.0. As a result, 181 genes were shown to be differentially expressed between experimental groups. Among these, 10 genes, which significantly differ in Apert syndrome fibroblasts compared to controls, were shown to be involved in a common interaction network and have common Gene ontology (GO) biological processes terms. COL11A1, COMP, CPXM2, ITGA8, MGF and TNC are differentially expressed genes that have GO terms associated with extracellular matrix (ECM) organization, while FRZB, SFRP2 and WNT2 are involved in WNT signaling pathway. Reorganization of ECM and changes in WNT signaling pathway show that Apert syndrome primary fibroblast cultures may have an increased potential for bone differentiation. The results of this study support craniosynostosis in Apert syndrome may be the result of fast and early differentiation of connective tissue along the sutures. https://turkjpediatr.org/article/view/1043Apert syndromecraniosynostosisfibroblastfibroblast growth factor receptor type 2transcriptome |
| spellingShingle | Arda Çetinkaya Ekim Taşkıran Tutku Soyer Pelin Özlem Şimşek-Kiper Gülen Eda Utine Gökhan Tunçbilek Koray Boduroğlu Mehmet Alikaşifoğlu Dermal fibroblast transcriptome indicates contribution of WNT signaling pathways in the pathogenesis of Apert syndrome The Turkish Journal of Pediatrics Apert syndrome craniosynostosis fibroblast fibroblast growth factor receptor type 2 transcriptome |
| title | Dermal fibroblast transcriptome indicates contribution of WNT signaling pathways in the pathogenesis of Apert syndrome |
| title_full | Dermal fibroblast transcriptome indicates contribution of WNT signaling pathways in the pathogenesis of Apert syndrome |
| title_fullStr | Dermal fibroblast transcriptome indicates contribution of WNT signaling pathways in the pathogenesis of Apert syndrome |
| title_full_unstemmed | Dermal fibroblast transcriptome indicates contribution of WNT signaling pathways in the pathogenesis of Apert syndrome |
| title_short | Dermal fibroblast transcriptome indicates contribution of WNT signaling pathways in the pathogenesis of Apert syndrome |
| title_sort | dermal fibroblast transcriptome indicates contribution of wnt signaling pathways in the pathogenesis of apert syndrome |
| topic | Apert syndrome craniosynostosis fibroblast fibroblast growth factor receptor type 2 transcriptome |
| url | https://turkjpediatr.org/article/view/1043 |
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