{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T14:00:39Z","timestamp":1780322439076,"version":"3.54.1"},"reference-count":14,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,5,5]],"date-time":"2023-05-05T00:00:00Z","timestamp":1683244800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003478","name":"Ministry of Health, Labour and Welfare","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003478","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>The Ehlers\u2013Danlos Syndromes (EDS), a group of hereditary connective tissue disorders, were classified into 13 subtypes in the 2017 International Classification. Recently, a new subtype of EDS called classical-like EDS type 2 (clEDS2), which is caused by biallelic variants in the adipocyte enhancer binding protein 1 (<jats:italic>AEBP1<\/jats:italic>) gene, was identified. We describe the 11th patient (9th family) with clEDS2, who was complicated by a critical vascular event (superior mesenteric artery aneurysm and rupture). A next-generation sequencing panel-based analysis revealed compound heterozygous variants in <jats:italic>AEBP1<\/jats:italic>: NM_001129.5:c.[2296G&amp;gt;T]; [2383dup], p.[(Glu766*)]; [(Glu795Glyfs*3)]. Light microscopic analyses showed increased interfibrillar spaces in the reticular dermis, a disorganized arrangement of collagen fibers, and decreased collagen content. An electron microscopic analysis showed the presence of collagen fibrils with irregular contours (flower-like appearance) and small collagen fibrils. A biochemical analysis showed reduced secretion of type I and type III procollagen. Clinical and molecular features of the current patient and all previously reported patients were reviewed comprehensively. Manifestations noted in most cases (&amp;gt;80%) included skin features (hyperextensibility, atrophic scars, easy bruising, excessive skin\/skin folding, delayed wound healing, translucency, piezogenic papules), skeletal features (generalized joint hypermobility, dislocations\/subluxations, pes planus), dental abnormalities, and neuromuscular abnormalities. Critical complications, each occurring in a single case, included superior mesenteric artery multiple aneurysm and rupture, aortic root dilation requiring surgery, and bowel rupture. Most <jats:italic>AEBP1<\/jats:italic> variants were predicted or experimentally confirmed to lead to nonsense-mediated mRNA decay, whereas one variant resulted in a protein that was retained intracellularly and not secreted. Clinical, molecular, pathological, and biochemical features of the current patient, as well as a review of all previously reported patients, suggest the importance of the aortic carboxypeptidase-like protein encoded by <jats:italic>AEBP1<\/jats:italic> in collagen fibrillogenesis.<\/jats:p>","DOI":"10.3389\/fgene.2023.1102101","type":"journal-article","created":{"date-parts":[[2023,5,5]],"date-time":"2023-05-05T08:46:58Z","timestamp":1683276418000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Case report: further delineation of AEBP1-related Ehlers\u2013Danlos Syndrome (classical-like EDS type 2) in an additional patient and comprehensive clinical and molecular review of the literature"],"prefix":"10.3389","volume":"14","author":[{"given":"Tomomi","family":"Yamaguchi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shujiro","family":"Hayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"So","family":"Nagai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiko","family":"Uchiyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sei-Ichiro","family":"Motegi","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":"Tomoki","family":"Kosho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,5,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1007\/s00439-016-1660-z","article-title":"Expanding the clinical and genetic heterogeneity of hereditary disorders of connective tissue","volume":"135","author":"Alazami","year":"2016","journal-title":"Hum. 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