{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T22:12:32Z","timestamp":1783980752883,"version":"3.55.0"},"reference-count":49,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,5,11]],"date-time":"2021-05-11T00:00:00Z","timestamp":1620691200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health","award":["CCR-2017-23669081"],"award-info":[{"award-number":["CCR-2017-23669081"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Junctional epidermolysis bullosa (JEB) is a clinically and genetically heterogeneous skin fragility disorder frequently caused by mutations in genes encoding the epithelial laminin isoform, laminin-332. JEB patients also present mucosal involvement, including painful corneal lesions. Recurrent corneal abrasions may lead to corneal opacities and visual impairment. Current treatments are merely supportive. We report a novel JEB phenotype distinguished by the complete resolution of skin fragility in infancy and persistent ocular involvement with unremitting and painful corneal abrasions. Biallelic LAMB3 mutations c.3052-5C&gt;G and c.3492_3493delCG were identified as the molecular basis for this phenotype, with one mutation being a hypomorphic splice variant that allows residual wild-type laminin-332 production. The reduced laminin-332 level was associated with impaired keratinocyte adhesion. Then, we also investigated the therapeutic power of a human amniotic membrane (AM) eyedrop preparation for corneal lesions. AM were isolated from placenta donors, according to a procedure preserving the AM biological characteristics as a tissue, and confirmed to contain laminin-332. We found that AM eyedrop preparation could restore keratinocyte adhesion in an in vitro assay. Of note, AM eyedrop administration to the patient resulted in long-lasting remission of her ocular manifestations. Our findings suggest that AM eyedrops could represent an effective, non-invasive, simple-to-handle treatment for corneal lesions in patients with JEB and possibly other EB forms.<\/jats:p>","DOI":"10.3390\/genes12050716","type":"journal-article","created":{"date-parts":[[2021,5,11]],"date-time":"2021-05-11T11:30:16Z","timestamp":1620732616000},"page":"716","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["A Novel Phenotype of Junctional Epidermolysis Bullosa with Transient Skin Fragility and Predominant Ocular Involvement Responsive to Human Amniotic Membrane Eyedrops"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3501-6742","authenticated-orcid":false,"given":"Daniele","family":"Castiglia","sequence":"first","affiliation":[{"name":"Laboratory of Molecular and Cell Biology, IDI-IRCCS, 00167 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0151-6477","authenticated-orcid":false,"given":"Paola","family":"Fortugno","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cell Biology, IDI-IRCCS, 00167 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1502-5852","authenticated-orcid":false,"given":"Angelo Giuseppe","family":"Condorelli","sequence":"additional","affiliation":[{"name":"Genodermatosis Unit, Genetics and Rare Diseases Research Division, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7307-388X","authenticated-orcid":false,"given":"Sabina","family":"Barresi","sequence":"additional","affiliation":[{"name":"Genetics and Rare Diseases Research Division, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi","family":"De Luca","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cell Biology, IDI-IRCCS, 00167 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Pizzi","sequence":"additional","affiliation":[{"name":"Genetics and Rare Diseases Research Division, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iria","family":"Neri","sequence":"additional","affiliation":[{"name":"Department of Experimental, Diagnostic and Specialty Medicine, Division of Dermatology, S. Orsola-Malpighi University Hospital, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3875-6869","authenticated-orcid":false,"given":"Claudio","family":"Graziano","sequence":"additional","affiliation":[{"name":"Medical Genetics, S. Orsola-Malpighi University Hospital, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9003-9421","authenticated-orcid":false,"given":"Diletta","family":"Trojan","sequence":"additional","affiliation":[{"name":"Treviso Tissue Bank Foundation, 31100 Treviso, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6038-3977","authenticated-orcid":false,"given":"Diego","family":"Ponzin","sequence":"additional","affiliation":[{"name":"The Veneto Eye Bank Foundation, 30174 Venice, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Rossi","sequence":"additional","affiliation":[{"name":"Pathology Unit, Department of Laboratories, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Zambruno","sequence":"additional","affiliation":[{"name":"Genodermatosis Unit, Genetics and Rare Diseases Research Division, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Tartaglia","sequence":"additional","affiliation":[{"name":"Genetics and Rare Diseases Research Division, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.matbio.2018.04.001","article-title":"Epidermolysis bullosa: Molecular pathology of connective tissue components in the cutaneous basement membrane zone","volume":"71\u201372","author":"Has","year":"2018","journal-title":"Matrix Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1111\/bjd.18921","article-title":"Consensus reclassification of inherited epidermolysis bullosa and other disorders with skin fragility","volume":"183","author":"Has","year":"2020","journal-title":"Br. 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