{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T05:06:52Z","timestamp":1784005612974,"version":"3.55.0"},"reference-count":24,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T00:00:00Z","timestamp":1693353600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>Classical-like Ehlers\u2013Danlos syndrome (clEDS) is an autosomal recessive disorder caused by complete absence of tenascin-X resulting from biallelic variation in <jats:italic>TNXB<\/jats:italic>. Thus far, 50 patients from 43 families with biallelic <jats:italic>TNXB<\/jats:italic> variants have been identified. Accurate detection of <jats:italic>TNXB<\/jats:italic> variants is challenging because of the presence of the pseudogene <jats:italic>TNXA<\/jats:italic>, 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 <jats:italic>TNXB<\/jats:italic> variants and the recombination of <jats:italic>TNXA<\/jats:italic>-derived sequences into <jats:italic>TNXB<\/jats:italic>. Using this system, we identified biallelic <jats:italic>TNXB<\/jats:italic> variants in nine unrelated clEDS patients. <jats:italic>TNXA<\/jats:italic>-derived variations were found in &amp;gt;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 <jats:italic>TNXB<\/jats:italic> variants and represents the third largest cohort of clEDS, highlighting the importance of increasing awareness of the risk of gastrointestinal complications.<\/jats:p>","DOI":"10.3389\/fgene.2023.1234804","type":"journal-article","created":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T13:20:33Z","timestamp":1693401633000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Clinical and molecular delineation of classical-like Ehlers\u2013Danlos syndrome through a comprehensive next-generation sequencing-based screening system"],"prefix":"10.3389","volume":"14","author":[{"given":"Tomomi","family":"Yamaguchi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuo","family":"Yamada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"So","family":"Nagai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiya","family":"Nishikubo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norimichi","family":"Koitabashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masako","family":"Minami-Hori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaaki","family":"Matsushima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuka","family":"Shibata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Ishiguro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromi","family":"Sanai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomomi","family":"Fujikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuri","family":"Takiguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken-Ichi","family":"Matsumoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoki","family":"Kosho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,8,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"618","DOI":"10.1002\/ajmg.a.62539","article-title":"Rare neurological manifestations in a Saudi Arabian patient with Ehlers\u2013Danlos syndrome and a novel homozygous variant in the TNXB gene","volume":"188","author":"Al-Harbi","year":"2022","journal-title":"Am. 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