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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
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.
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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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