A Novel Phenotype of Junctional Epidermolysis Bullosa with Transient Skin Fragility and Predominant Ocular Involvement Responsive to Human Amniotic Membrane Eyedrops
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 corne...
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| Veröffentlicht in: | Genes 2021-05, Vol.12 (5), p.716 |
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| creator | Castiglia, Daniele Fortugno, Paola Condorelli, Angelo Giuseppe Barresi, Sabina De Luca, Naomi Pizzi, Simone Neri, Iria Graziano, Claudio Trojan, Diletta Ponzin, Diego Rossi, Sabrina Zambruno, Giovanna Tartaglia, Marco |
| description | 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
mutations c.3052-5C>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. |
| doi_str_mv | 10.3390/genes12050716 |
| format | Article |
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mutations c.3052-5C>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.</description><identifier>ISSN: 2073-4425</identifier><identifier>EISSN: 2073-4425</identifier><identifier>DOI: 10.3390/genes12050716</identifier><identifier>PMID: 34064633</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Alternative splicing ; Amnion - chemistry ; Amniotic membrane ; Biopsy ; Cell Adhesion ; Cell Adhesion Molecules - genetics ; Cells, Cultured ; Child, Preschool ; Cornea ; Corneal Dystrophies, Hereditary - drug therapy ; Corneal Dystrophies, Hereditary - genetics ; Corneal Dystrophies, Hereditary - pathology ; Disease ; Epidermolysis bullosa ; Epidermolysis Bullosa, Junctional - drug therapy ; Epidermolysis Bullosa, Junctional - genetics ; Epidermolysis Bullosa, Junctional - pathology ; Epithelium, Corneal - pathology ; Extracellular matrix ; Eye ; Female ; Genotype & phenotype ; Humans ; Junctional epidermolysis bullosa ; Kalinin ; Keratinocytes - drug effects ; Keratinocytes - pathology ; Keratinocytes - physiology ; Laminin ; Lesions ; Mucosa ; Mutation ; Ophthalmic Solutions - chemistry ; Ophthalmic Solutions - pharmacology ; Ophthalmic Solutions - therapeutic use ; Phenotype ; Phenotypes ; Placenta ; Remission ; Skin ; Skin - pathology</subject><ispartof>Genes, 2021-05, Vol.12 (5), p.716</ispartof><rights>2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). 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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
mutations c.3052-5C>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.</description><subject>Alternative splicing</subject><subject>Amnion - chemistry</subject><subject>Amniotic membrane</subject><subject>Biopsy</subject><subject>Cell Adhesion</subject><subject>Cell Adhesion Molecules - genetics</subject><subject>Cells, Cultured</subject><subject>Child, Preschool</subject><subject>Cornea</subject><subject>Corneal Dystrophies, Hereditary - drug therapy</subject><subject>Corneal Dystrophies, Hereditary - genetics</subject><subject>Corneal Dystrophies, Hereditary - pathology</subject><subject>Disease</subject><subject>Epidermolysis bullosa</subject><subject>Epidermolysis Bullosa, Junctional - drug therapy</subject><subject>Epidermolysis Bullosa, Junctional - genetics</subject><subject>Epidermolysis Bullosa, Junctional - pathology</subject><subject>Epithelium, Corneal - pathology</subject><subject>Extracellular matrix</subject><subject>Eye</subject><subject>Female</subject><subject>Genotype & phenotype</subject><subject>Humans</subject><subject>Junctional epidermolysis bullosa</subject><subject>Kalinin</subject><subject>Keratinocytes - 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chemistry</topic><topic>Amniotic membrane</topic><topic>Biopsy</topic><topic>Cell Adhesion</topic><topic>Cell Adhesion Molecules - genetics</topic><topic>Cells, Cultured</topic><topic>Child, Preschool</topic><topic>Cornea</topic><topic>Corneal Dystrophies, Hereditary - drug therapy</topic><topic>Corneal Dystrophies, Hereditary - genetics</topic><topic>Corneal Dystrophies, Hereditary - pathology</topic><topic>Disease</topic><topic>Epidermolysis bullosa</topic><topic>Epidermolysis Bullosa, Junctional - drug therapy</topic><topic>Epidermolysis Bullosa, Junctional - genetics</topic><topic>Epidermolysis Bullosa, Junctional - pathology</topic><topic>Epithelium, Corneal - pathology</topic><topic>Extracellular matrix</topic><topic>Eye</topic><topic>Female</topic><topic>Genotype & phenotype</topic><topic>Humans</topic><topic>Junctional epidermolysis bullosa</topic><topic>Kalinin</topic><topic>Keratinocytes - drug effects</topic><topic>Keratinocytes - pathology</topic><topic>Keratinocytes - physiology</topic><topic>Laminin</topic><topic>Lesions</topic><topic>Mucosa</topic><topic>Mutation</topic><topic>Ophthalmic Solutions - chemistry</topic><topic>Ophthalmic Solutions - pharmacology</topic><topic>Ophthalmic Solutions - therapeutic use</topic><topic>Phenotype</topic><topic>Phenotypes</topic><topic>Placenta</topic><topic>Remission</topic><topic>Skin</topic><topic>Skin - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Castiglia, Daniele</creatorcontrib><creatorcontrib>Fortugno, Paola</creatorcontrib><creatorcontrib>Condorelli, Angelo Giuseppe</creatorcontrib><creatorcontrib>Barresi, Sabina</creatorcontrib><creatorcontrib>De Luca, Naomi</creatorcontrib><creatorcontrib>Pizzi, Simone</creatorcontrib><creatorcontrib>Neri, Iria</creatorcontrib><creatorcontrib>Graziano, Claudio</creatorcontrib><creatorcontrib>Trojan, Diletta</creatorcontrib><creatorcontrib>Ponzin, Diego</creatorcontrib><creatorcontrib>Rossi, Sabrina</creatorcontrib><creatorcontrib>Zambruno, Giovanna</creatorcontrib><creatorcontrib>Tartaglia, Marco</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Genes</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Castiglia, Daniele</au><au>Fortugno, Paola</au><au>Condorelli, Angelo Giuseppe</au><au>Barresi, Sabina</au><au>De Luca, Naomi</au><au>Pizzi, Simone</au><au>Neri, Iria</au><au>Graziano, Claudio</au><au>Trojan, Diletta</au><au>Ponzin, Diego</au><au>Rossi, Sabrina</au><au>Zambruno, Giovanna</au><au>Tartaglia, Marco</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Novel Phenotype of Junctional Epidermolysis Bullosa with Transient Skin Fragility and Predominant Ocular Involvement Responsive to Human Amniotic Membrane Eyedrops</atitle><jtitle>Genes</jtitle><addtitle>Genes (Basel)</addtitle><date>2021-05-11</date><risdate>2021</risdate><volume>12</volume><issue>5</issue><spage>716</spage><pages>716-</pages><issn>2073-4425</issn><eissn>2073-4425</eissn><abstract>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
mutations c.3052-5C>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.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>34064633</pmid><doi>10.3390/genes12050716</doi><orcidid>https://orcid.org/0000-0003-3501-6742</orcidid><orcidid>https://orcid.org/0000-0002-7307-388X</orcidid><orcidid>https://orcid.org/0000-0002-9003-9421</orcidid><orcidid>https://orcid.org/0000-0003-1502-5852</orcidid><orcidid>https://orcid.org/0000-0002-6038-3977</orcidid><orcidid>https://orcid.org/0000-0002-0151-6477</orcidid><orcidid>https://orcid.org/0000-0003-3875-6869</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Genes, 2021-05, Vol.12 (5), p.716 |
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| subjects | Alternative splicing Amnion - chemistry Amniotic membrane Biopsy Cell Adhesion Cell Adhesion Molecules - genetics Cells, Cultured Child, Preschool Cornea Corneal Dystrophies, Hereditary - drug therapy Corneal Dystrophies, Hereditary - genetics Corneal Dystrophies, Hereditary - pathology Disease Epidermolysis bullosa Epidermolysis Bullosa, Junctional - drug therapy Epidermolysis Bullosa, Junctional - genetics Epidermolysis Bullosa, Junctional - pathology Epithelium, Corneal - pathology Extracellular matrix Eye Female Genotype & phenotype Humans Junctional epidermolysis bullosa Kalinin Keratinocytes - drug effects Keratinocytes - pathology Keratinocytes - physiology Laminin Lesions Mucosa Mutation Ophthalmic Solutions - chemistry Ophthalmic Solutions - pharmacology Ophthalmic Solutions - therapeutic use Phenotype Phenotypes Placenta Remission Skin Skin - pathology |
| title | A Novel Phenotype of Junctional Epidermolysis Bullosa with Transient Skin Fragility and Predominant Ocular Involvement Responsive to Human Amniotic Membrane Eyedrops |
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