{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T13:56:42Z","timestamp":1780322202430,"version":"3.54.1"},"reference-count":20,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,12,14]],"date-time":"2022-12-14T00:00:00Z","timestamp":1670976000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Sapienza University of Rome, \u201cAvvio alla Ricerca tipo 1\u201d project","award":["AR12117A5BCBB73F"],"award-info":[{"award-number":["AR12117A5BCBB73F"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>In 2018, a new clinical subtype, caused by biallelic variants in the AEBP1 gene, encoding the ACLP protein, was added to the current nosological classification of the Ehlers\u2013Danlos Syndromes (EDS). This new phenotype, provisionally termed EDS classical-like type 2 (clEDS2), has not yet been fully characterized, as only nine cases have been reported to date. Here we describe a patient, homozygous for a novel AEBP1 pathogenic variant (NM_001129.5 c.2123_2124delTG (p.Val708AlafsTer5)), whose phenotype is reminiscent of classical EDS but also includes previously unreported multiple congenital malformations. Furthermore, we briefly summarize the current principal clinical manifestations of clEDS2 and the molecular evidence surrounding the role of AEBP1 in the context of extracellular matrix homeostasis and connective tissue development. Although a different coexisting etiology for the multiple congenital malformations of our patient cannot be formally excluded, the emerging role of ACLP in TGF-\u03b2 and WNT pathways may explain their occurrence and the phenotypical variability of clEDS2.<\/jats:p>","DOI":"10.3390\/genes13122358","type":"journal-article","created":{"date-parts":[[2022,12,14]],"date-time":"2022-12-14T04:54:49Z","timestamp":1670993689000},"page":"2358","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Congenital Defects in a Patient Carrying a Novel Homozygous AEBP1 Variant: Further Expansion of the Phenotypic Spectrum of Ehlers\u2013Danlos Syndrome Classical-like Type 2?"],"prefix":"10.3390","volume":"13","author":[{"given":"Niccol\u00f2","family":"Di Giosaffatte","sequence":"first","affiliation":[{"name":"Laboratory of Medical Genetics, Department of Experimental Medicine, San Camillo-Forlanini Hospital, Sapienza University, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2947-9572","authenticated-orcid":false,"given":"Alessandro","family":"Ferraris","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics, Department of Experimental Medicine, San Camillo-Forlanini Hospital, Sapienza University, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Gaudioso","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics, Department of Experimental Medicine, San Camillo-Forlanini Hospital, Sapienza University, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Lodato","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics, Department of Experimental Medicine, San Camillo-Forlanini Hospital, Sapienza University, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuele","family":"Savino","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics, Department of Experimental Medicine, San Camillo-Forlanini Hospital, Sapienza University, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7154-5882","authenticated-orcid":false,"given":"Claudia","family":"Celletti","sequence":"additional","affiliation":[{"name":"Physical Medicine and Rehabilitation Division, Umberto I University Hospital of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippo","family":"Camerota","sequence":"additional","affiliation":[{"name":"Physical Medicine and Rehabilitation Division, Umberto I University Hospital of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5276-7500","authenticated-orcid":false,"given":"Simone","family":"Bargiacchi","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics, Department of Experimental Medicine, San Camillo-Forlanini Hospital, Sapienza University, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Laino","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics, Department of Experimental Medicine, San Camillo-Forlanini Hospital, Sapienza University, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Majore","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics, Department of Experimental Medicine, San Camillo-Forlanini Hospital, Sapienza University, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0396-7981","authenticated-orcid":false,"given":"Irene","family":"Bottillo","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics, Department of Experimental Medicine, San Camillo-Forlanini Hospital, Sapienza University, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Grammatico","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics, Department of Experimental Medicine, San Camillo-Forlanini Hospital, Sapienza University, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1002\/ajmg.c.31552","article-title":"The 2017 international classification of the Ehlers-Danlos syndromes","volume":"175","author":"Malfait","year":"2017","journal-title":"Am. 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