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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...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10498456/ https://www.ncbi.nlm.nih.gov/pubmed/37712068 http://dx.doi.org/10.3389/fgene.2023.1234804 |
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author | Yamaguchi, Tomomi Yamada, Kazuo Nagai, So Nishikubo, Toshiya Koitabashi, Norimichi Minami-Hori, Masako Matsushima, Masaaki Shibata, Yuka Ishiguro, Hiroki Sanai, Hiromi Fujikawa, Tomomi Takiguchi, Yuri Matsumoto, Ken-Ichi Kosho, Tomoki |
author_facet | Yamaguchi, Tomomi Yamada, Kazuo Nagai, So Nishikubo, Toshiya Koitabashi, Norimichi Minami-Hori, Masako Matsushima, Masaaki Shibata, Yuka Ishiguro, Hiroki Sanai, Hiromi Fujikawa, Tomomi Takiguchi, Yuri Matsumoto, Ken-Ichi Kosho, Tomoki |
author_sort | Yamaguchi, Tomomi |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-10498456 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-104984562023-09-14 Clinical and molecular delineation of classical-like Ehlers–Danlos syndrome through a comprehensive next-generation sequencing-based screening system Yamaguchi, Tomomi Yamada, Kazuo Nagai, So Nishikubo, Toshiya Koitabashi, Norimichi Minami-Hori, Masako Matsushima, Masaaki Shibata, Yuka Ishiguro, Hiroki Sanai, Hiromi Fujikawa, Tomomi Takiguchi, Yuri Matsumoto, Ken-Ichi Kosho, Tomoki Front Genet Genetics 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. Frontiers Media S.A. 2023-08-30 /pmc/articles/PMC10498456/ /pubmed/37712068 http://dx.doi.org/10.3389/fgene.2023.1234804 Text en Copyright © 2023 Yamaguchi, Yamada, Nagai, Nishikubo, Koitabashi, Minami-Hori, Matsushima, Shibata, Ishiguro, Sanai, Fujikawa, Takiguchi, Matsumoto and Kosho. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Genetics Yamaguchi, Tomomi Yamada, Kazuo Nagai, So Nishikubo, Toshiya Koitabashi, Norimichi Minami-Hori, Masako Matsushima, Masaaki Shibata, Yuka Ishiguro, Hiroki Sanai, Hiromi Fujikawa, Tomomi Takiguchi, Yuri Matsumoto, Ken-Ichi Kosho, Tomoki Clinical and molecular delineation of classical-like Ehlers–Danlos syndrome through a comprehensive next-generation sequencing-based screening system |
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 | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10498456/ https://www.ncbi.nlm.nih.gov/pubmed/37712068 http://dx.doi.org/10.3389/fgene.2023.1234804 |
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