Clinical and molecular delineation of classical-like Ehlers–Danlos syndrome through a comprehensive next-generation sequencing-based screening system
Classical-like Ehlers–Danlos syndrome (clEDS) is an autosomal recessive disorder caused by complete absence of tenascin-X resulting from biallelic variation in TNXB. Thus far, 50 patients from 43 families with biallelic TNXB variants have been identified. Accurate detection of TNXB variants is chall...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-08-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2023.1234804/full |
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| author | Tomomi Yamaguchi Tomomi Yamaguchi Tomomi Yamaguchi Kazuo Yamada Kazuo Yamada So Nagai So Nagai So Nagai Toshiya Nishikubo Norimichi Koitabashi Masako Minami-Hori Masaaki Matsushima Masaaki Matsushima Yuka Shibata Hiroki Ishiguro Hiromi Sanai Hiromi Sanai Tomomi Fujikawa Yuri Takiguchi Ken-Ichi Matsumoto Tomoki Kosho Tomoki Kosho Tomoki Kosho Tomoki Kosho |
| author_facet | Tomomi Yamaguchi Tomomi Yamaguchi Tomomi Yamaguchi Kazuo Yamada Kazuo Yamada So Nagai So Nagai So Nagai Toshiya Nishikubo Norimichi Koitabashi Masako Minami-Hori Masaaki Matsushima Masaaki Matsushima Yuka Shibata Hiroki Ishiguro Hiromi Sanai Hiromi Sanai Tomomi Fujikawa Yuri Takiguchi Ken-Ichi Matsumoto Tomoki Kosho Tomoki Kosho Tomoki Kosho Tomoki Kosho |
| author_sort | Tomomi Yamaguchi |
| collection | DOAJ |
| description | Classical-like Ehlers–Danlos syndrome (clEDS) is an autosomal recessive disorder caused by complete absence of tenascin-X resulting from biallelic variation in TNXB. Thus far, 50 patients from 43 families with biallelic TNXB variants have been identified. Accurate detection of TNXB variants is challenging because of the presence of the pseudogene TNXA, which can undergo non-allelic homologous recombination. Therefore, we designed a genetic screening system that is performed using similar operations to other next-generation sequencing (NGS) panel analyses and can be applied to accurately detect TNXB variants and the recombination of TNXA-derived sequences into TNXB. Using this system, we identified biallelic TNXB variants in nine unrelated clEDS patients. TNXA-derived variations were found in >75% of the current cohort, comparable to previous reports. The current cohort generally exhibited similar clinical features to patients in previous reports, but had a higher frequency of gastrointestinal complications (e.g., perforation, diverticulitis, gastrointestinal bleeding, intestinal obstruction, rectal/anal prolapse, and gallstones). This report is the first to apply an NGS-based screening for TNXB variants and represents the third largest cohort of clEDS, highlighting the importance of increasing awareness of the risk of gastrointestinal complications. |
| first_indexed | 2024-03-12T12:15:53Z |
| format | Article |
| id | doaj.art-771a1d3030c643ce8f073f734a1aa288 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-03-12T12:15:53Z |
| publishDate | 2023-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-771a1d3030c643ce8f073f734a1aa2882023-08-30T13:24:03ZengFrontiers Media S.A.Frontiers in Genetics1664-80212023-08-011410.3389/fgene.2023.12348041234804Clinical and molecular delineation of classical-like Ehlers–Danlos syndrome through a comprehensive next-generation sequencing-based screening systemTomomi Yamaguchi0Tomomi Yamaguchi1Tomomi Yamaguchi2Kazuo Yamada3Kazuo Yamada4So Nagai5So Nagai6So Nagai7Toshiya Nishikubo8Norimichi Koitabashi9Masako Minami-Hori10Masaaki Matsushima11Masaaki Matsushima12Yuka Shibata13Hiroki Ishiguro14Hiromi Sanai15Hiromi Sanai16Tomomi Fujikawa17Yuri Takiguchi18Ken-Ichi Matsumoto19Tomoki Kosho20Tomoki Kosho21Tomoki Kosho22Tomoki Kosho23Center for Medical Genetics, Shinshu University Hospital, Matsumoto, JapanDepartment of Medical Genetics, Shinshu University School of Medicine, Matsumoto, JapanDivision of Clinical Sequencing, Shinshu University School of Medicine, Matsumoto, JapanDepartment of Biosignaling and Radioisotope Experiment, Interdisciplinary Center for Science Research, Head Office for Research and Academic Information, Shimane University, Izumo, JapanDepartment of Legal Medicine, Faculty of Medicine, Shimane University, Izumo, JapanCenter for Medical Genetics, Shinshu University Hospital, Matsumoto, JapanDivision of Clinical Sequencing, Shinshu University School of Medicine, Matsumoto, JapanProblem-Solving Oriented Training Program for Advanced Medical Personnel: NGSD (Next-Generation Super Doctor) Project, Matsumoto, JapanDivision of Neonatal Intensive Care, Nara Medical University, Nara, JapanDepartment of Cardiovascular Medicine, Gunma University Graduate School of Medicine, Maebashi, JapanDivision of Dermatology, Asahikawa City Hospital, Asahikawa, Japan0Department of Neurology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan1Division of Clinical Genetics, Hokkaido University Hospital, Sapporo, Japan1Division of Clinical Genetics, Hokkaido University Hospital, Sapporo, Japan2Department of Clinical Genetics, Graduate School of Medicine, University of Yamanashi, Chuo, Japan3Department of Obstetrics and Gynecology, Yamaguchi Prefectural Grand Medical Center, Yamaguchi, Japan4Department of Medical Genetics, Yamaguchi Prefectural Grand Medical Center, Yamaguchi, JapanDivision of Clinical Sequencing, Shinshu University School of Medicine, Matsumoto, JapanDivision of Clinical Sequencing, Shinshu University School of Medicine, Matsumoto, JapanDepartment of Biosignaling and Radioisotope Experiment, Interdisciplinary Center for Science Research, Head Office for Research and Academic Information, Shimane University, Izumo, JapanCenter for Medical Genetics, Shinshu University Hospital, Matsumoto, JapanDepartment of Medical Genetics, Shinshu University School of Medicine, Matsumoto, JapanDivision of Clinical Sequencing, Shinshu University School of Medicine, Matsumoto, Japan5Research Center for Supports to Advanced Science, Shinshu University, Matsumoto, JapanClassical-like Ehlers–Danlos syndrome (clEDS) is an autosomal recessive disorder caused by complete absence of tenascin-X resulting from biallelic variation in TNXB. Thus far, 50 patients from 43 families with biallelic TNXB variants have been identified. Accurate detection of TNXB variants is challenging because of the presence of the pseudogene TNXA, which can undergo non-allelic homologous recombination. Therefore, we designed a genetic screening system that is performed using similar operations to other next-generation sequencing (NGS) panel analyses and can be applied to accurately detect TNXB variants and the recombination of TNXA-derived sequences into TNXB. Using this system, we identified biallelic TNXB variants in nine unrelated clEDS patients. TNXA-derived variations were found in >75% of the current cohort, comparable to previous reports. The current cohort generally exhibited similar clinical features to patients in previous reports, but had a higher frequency of gastrointestinal complications (e.g., perforation, diverticulitis, gastrointestinal bleeding, intestinal obstruction, rectal/anal prolapse, and gallstones). This report is the first to apply an NGS-based screening for TNXB variants and represents the third largest cohort of clEDS, highlighting the importance of increasing awareness of the risk of gastrointestinal complications.https://www.frontiersin.org/articles/10.3389/fgene.2023.1234804/fullEhlers-Danlos syndromeclassical-likeTNXBtenascin-Xconnective tissue disorder |
| spellingShingle | Tomomi Yamaguchi Tomomi Yamaguchi Tomomi Yamaguchi Kazuo Yamada Kazuo Yamada So Nagai So Nagai So Nagai Toshiya Nishikubo Norimichi Koitabashi Masako Minami-Hori Masaaki Matsushima Masaaki Matsushima Yuka Shibata Hiroki Ishiguro Hiromi Sanai Hiromi Sanai Tomomi Fujikawa Yuri Takiguchi Ken-Ichi Matsumoto Tomoki Kosho Tomoki Kosho Tomoki Kosho Tomoki Kosho Clinical and molecular delineation of classical-like Ehlers–Danlos syndrome through a comprehensive next-generation sequencing-based screening system Frontiers in Genetics Ehlers-Danlos syndrome classical-like TNXB tenascin-X connective tissue disorder |
| title | Clinical and molecular delineation of classical-like Ehlers–Danlos syndrome through a comprehensive next-generation sequencing-based screening system |
| title_full | Clinical and molecular delineation of classical-like Ehlers–Danlos syndrome through a comprehensive next-generation sequencing-based screening system |
| title_fullStr | Clinical and molecular delineation of classical-like Ehlers–Danlos syndrome through a comprehensive next-generation sequencing-based screening system |
| title_full_unstemmed | Clinical and molecular delineation of classical-like Ehlers–Danlos syndrome through a comprehensive next-generation sequencing-based screening system |
| title_short | Clinical and molecular delineation of classical-like Ehlers–Danlos syndrome through a comprehensive next-generation sequencing-based screening system |
| title_sort | clinical and molecular delineation of classical like ehlers danlos syndrome through a comprehensive next generation sequencing based screening system |
| topic | Ehlers-Danlos syndrome classical-like TNXB tenascin-X connective tissue disorder |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2023.1234804/full |
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