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...
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Frontiers Media S.A.
2023-05-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2023.1102101/full |
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| author | Tomomi Yamaguchi Tomomi Yamaguchi Tomomi Yamaguchi Shujiro Hayashi So Nagai So Nagai Akihiko Uchiyama Sei-Ichiro Motegi Tomomi Fujikawa Yuri Takiguchi Tomoki Kosho Tomoki Kosho Tomoki Kosho Tomoki Kosho |
| author_facet | Tomomi Yamaguchi Tomomi Yamaguchi Tomomi Yamaguchi Shujiro Hayashi So Nagai So Nagai Akihiko Uchiyama Sei-Ichiro Motegi Tomomi Fujikawa Yuri Takiguchi Tomoki Kosho Tomoki Kosho Tomoki Kosho Tomoki Kosho |
| author_sort | Tomomi Yamaguchi |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-09T14:15:58Z |
| format | Article |
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| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-09T14:15:58Z |
| publishDate | 2023-05-01 |
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| series | Frontiers in Genetics |
| spelling | doaj.art-1ff3241ae08b4512bdc48ea0b65d68202023-05-05T08:46:47ZengFrontiers Media S.A.Frontiers in Genetics1664-80212023-05-011410.3389/fgene.2023.11021011102101Case 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 literatureTomomi Yamaguchi0Tomomi Yamaguchi1Tomomi Yamaguchi2Shujiro Hayashi3So Nagai4So Nagai5Akihiko Uchiyama6Sei-Ichiro Motegi7Tomomi Fujikawa8Yuri Takiguchi9Tomoki Kosho10Tomoki Kosho11Tomoki Kosho12Tomoki Kosho13Center for Medical Genetics, Shinshu University Hospital, Matsumoto, JapanDepartment of Medical Genetics, Shinshu University School of Medicine, Matsumoto, JapanDivision of Clinical Sequencing, Shinshu University School of Medicine, Matsumoto, JapanDepartment of Dermatology, Dokkyo Medical University, Mibu, JapanCenter for Medical Genetics, Shinshu University Hospital, Matsumoto, JapanProblem-Solving Oriented Training Program for Advanced Medical Personnel: NGSD (Next-Generation Super Doctor) Project, Matsumoto, JapanDepartment of Dermatology, Gunma University Graduate School of Medicine, Maebashi, JapanDepartment of Dermatology, Gunma University Graduate School of Medicine, Maebashi, JapanDivision of Clinical Sequencing, Shinshu University School of Medicine, Matsumoto, JapanDivision of Clinical Sequencing, Shinshu University School of Medicine, Matsumoto, JapanCenter for Medical Genetics, Shinshu University Hospital, Matsumoto, JapanDepartment of Medical Genetics, Shinshu University School of Medicine, Matsumoto, JapanDivision of Clinical Sequencing, Shinshu University School of Medicine, Matsumoto, JapanResearch Center for Supports to Advanced Science, Shinshu University, Matsumoto, JapanThe 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.https://www.frontiersin.org/articles/10.3389/fgene.2023.1102101/fullEhlers-Danlos Syndromeclassical-like EDS type 2 (clEDS2)adipocyte enhancer binding protein 1 (AEBP1)aortic carboxypeptidase-like protein (ACLP)autosomal recessiveconnective tissue disorders |
| spellingShingle | Tomomi Yamaguchi Tomomi Yamaguchi Tomomi Yamaguchi Shujiro Hayashi So Nagai So Nagai Akihiko Uchiyama Sei-Ichiro Motegi Tomomi Fujikawa Yuri Takiguchi Tomoki Kosho Tomoki Kosho Tomoki Kosho Tomoki Kosho 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 Frontiers in Genetics Ehlers-Danlos Syndrome classical-like EDS type 2 (clEDS2) adipocyte enhancer binding protein 1 (AEBP1) aortic carboxypeptidase-like protein (ACLP) autosomal recessive connective tissue disorders |
| 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 | Ehlers-Danlos Syndrome classical-like EDS type 2 (clEDS2) adipocyte enhancer binding protein 1 (AEBP1) aortic carboxypeptidase-like protein (ACLP) autosomal recessive connective tissue disorders |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2023.1102101/full |
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