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Case report: further delineation of AEBP1-related Ehlers–Danlos Syndrome (classical-like EDS type 2) in an additional patient and comprehensive clinical and molecular review of the literature
The Ehlers–Danlos 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 b...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10196838/ https://www.ncbi.nlm.nih.gov/pubmed/37214418 http://dx.doi.org/10.3389/fgene.2023.1102101 |
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author | Yamaguchi, Tomomi Hayashi, Shujiro Nagai, So Uchiyama, Akihiko Motegi, Sei-Ichiro Fujikawa, Tomomi Takiguchi, Yuri Kosho, Tomoki |
author_facet | Yamaguchi, Tomomi Hayashi, Shujiro Nagai, So Uchiyama, Akihiko Motegi, Sei-Ichiro Fujikawa, Tomomi Takiguchi, Yuri Kosho, Tomoki |
author_sort | Yamaguchi, Tomomi |
collection | PubMed |
description | The Ehlers–Danlos 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 (AEBP1) 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 AEBP1: NM_001129.5:c.[2296G>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 (>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 AEBP1 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 AEBP1 in collagen fibrillogenesis. |
format | Online Article Text |
id | pubmed-10196838 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-101968382023-05-20 Case report: further delineation of AEBP1-related Ehlers–Danlos Syndrome (classical-like EDS type 2) in an additional patient and comprehensive clinical and molecular review of the literature Yamaguchi, Tomomi Hayashi, Shujiro Nagai, So Uchiyama, Akihiko Motegi, Sei-Ichiro Fujikawa, Tomomi Takiguchi, Yuri Kosho, Tomoki Front Genet Genetics The Ehlers–Danlos 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 (AEBP1) 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 AEBP1: NM_001129.5:c.[2296G>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 (>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 AEBP1 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 AEBP1 in collagen fibrillogenesis. Frontiers Media S.A. 2023-05-05 /pmc/articles/PMC10196838/ /pubmed/37214418 http://dx.doi.org/10.3389/fgene.2023.1102101 Text en Copyright © 2023 Yamaguchi, Hayashi, Nagai, Uchiyama, Motegi, Fujikawa, Takiguchi 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 Hayashi, Shujiro Nagai, So Uchiyama, Akihiko Motegi, Sei-Ichiro Fujikawa, Tomomi Takiguchi, Yuri Kosho, Tomoki Case report: further delineation of AEBP1-related Ehlers–Danlos Syndrome (classical-like EDS type 2) in an additional patient and comprehensive clinical and molecular review of the literature |
title | Case report: further delineation of AEBP1-related Ehlers–Danlos Syndrome (classical-like EDS type 2) in an additional patient and comprehensive clinical and molecular review of the literature |
title_full | Case report: further delineation of AEBP1-related Ehlers–Danlos Syndrome (classical-like EDS type 2) in an additional patient and comprehensive clinical and molecular review of the literature |
title_fullStr | Case report: further delineation of AEBP1-related Ehlers–Danlos Syndrome (classical-like EDS type 2) in an additional patient and comprehensive clinical and molecular review of the literature |
title_full_unstemmed | Case report: further delineation of AEBP1-related Ehlers–Danlos Syndrome (classical-like EDS type 2) in an additional patient and comprehensive clinical and molecular review of the literature |
title_short | Case report: further delineation of AEBP1-related Ehlers–Danlos Syndrome (classical-like EDS type 2) in an additional patient and comprehensive clinical and molecular review of the literature |
title_sort | case report: further delineation of aebp1-related ehlers–danlos syndrome (classical-like eds type 2) in an additional patient and comprehensive clinical and molecular review of the literature |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10196838/ https://www.ncbi.nlm.nih.gov/pubmed/37214418 http://dx.doi.org/10.3389/fgene.2023.1102101 |
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