Article
Agriculture, Dairy & Animal Science
Mekki Boussaha, Arnaud Boulling, Valerie Wolgust, Lorraine Bourgeois-Brunel, Pauline Michot, Cecile Grohs, Nicolas Gaiani, Pierre-Yves Grivaud, Helene Leclerc, Coralie Danchin-Burge, Marthe Vilotte, Julie Riviere, Didier Boichard, Jean-Marie Gourreau, Aurelien Capitan
Summary: A study found that Charolais calves have a congenital skin fragility disorder resembling inherited epidermolysis bullosa. Genetic analysis identified a mutation in the ITGA6 gene as the cause of this condition. This is the first evidence of an ITGA6 mutation causing EB in livestock species.
GENETICS SELECTION EVOLUTION
(2023)
Article
Medicine, General & Internal
Maximilian Kueckelhaus, Tobias Rothoeft, Laura De Rosa, Burcu Yeni, Tobias Ohmann, Christoph Maier, Lynn Eitner, Dieter Metze, Lorena Losi, Alessia Secone Seconetti, Michele De Luca, Tobias Hirsch
Summary: This study reports long-term clinical outcomes in a child with a severe genetic skin disease who received genetically corrected autologous epidermal cultures.
NEW ENGLAND JOURNAL OF MEDICINE
(2021)
Article
Biotechnology & Applied Microbiology
Johannes Bischof, Oliver Patrick March, Bernadette Liemberger, Simone Alexandra Haas, Stefan Hainzl, Igor Petkovic, Victoria Leb-Reichl, Julia Illmer, Evgeniia Korotchenko, Alfred Klausegger, Anna Hoog, Heide-Marie Binder, Marta Garcia, Blanca Duarte, Dirk Strunk, Fernando Larcher, Julia Reichelt, Christina Guttmann-Gruber, Verena Wally, Josefina Pinon Hofbauer, Johann Wolfgang Bauer, Toni Cathomen, Thomas Kocher, Ulrich Koller
Summary: This study successfully corrected a COL17A1 gene mutation associated with junctional epidermolysis bullosa using Cas9 nuclease and nickase-based targeting strategies. The corrected cells restored expression of C17 protein and showed improved adhesion capabilities. This research represents the first gene-editing-based correction of a COL17A1 mutation and demonstrates the superiority of proximal paired nicking strategies based on Cas9 D10A nickase for gene reframing in a clinical context.
Article
Multidisciplinary Sciences
Thomas J. Sproule, Robert Y. Wilpan, John J. Wilson, Benjamin E. Low, Yudai Kabata, Tatsuo Ushiki, Riichiro Abe, Michael V. Wiles, Derry C. Roopenian, John P. Sundberg
Summary: The study demonstrates the possibility of genetic modification of EB symptoms using the Lamc2jeb mouse model and identifies Col17a1 and other genetic loci as modifiers. Furthermore, CRISPR/Cas9 technology was used to alter a specific isoform of the dystonin gene in mice and validated a genetic difference as a modifier of EB. The study also reveals the potential of using mice with pinnae removed as a test bed for studying EB disease and treatment.
Article
Genetics & Heredity
Sarah Kiener, Heather Troyer, Daniel Ruvolo, Paula Grest, Sara Soto, Anna Letko, Vidhya Jagannathan, Tosso Leeb, Elizabeth A. Mauldin, Ching Yang, Ana Rostaher
Summary: Epidermolysis bullosa (EB) is a heterogeneous disease characterized by defective adhesion of the epidermis to the dermis. This study identified COL17A1 gene variants as the cause of EB in two cats, providing new insights into the diagnosis and genotype-phenotype correlation of this disease.
Article
Medicine, General & Internal
Igor Petkovic, Johannes Bischof, Thomas Kocher, Oliver Patrick March, Bernadette Liemberger, Stefan Hainzl, Dirk Strunk, Anna Maria Raninger, Heide-Marie Binder, Julia Reichelt, Christina Guttmann-Gruber, Verena Wally, Josefina Pinon Hofbauer, Johann Wolfgang Bauer, Ulrich Koller
Summary: In this study, researchers used CRISPR/Cas9 gene editing technique to successfully correct a causal pathogenic frameshift mutation in the COL17A1 gene, which leads to junctional epidermolysis bullosa. By inducing both end-joining repair and HDR-mediated pathways, they achieved efficient gene repair and observed improved cellular functions and structures in the corrected cells.
FRONTIERS IN MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Grace Tartaglia, Pyung Hun Park, Michael H. Alexander, Alexander Nystroem, Joel Rosenbloom, Andrew P. South
Summary: Junctional epidermolysis bullosa (JEB) is a skin disorder caused by a deficiency in genes associated with epidermal adhesion. Trametinib, a MEK inhibitor, can accelerate disease onset and decrease epidermal thickness in a mouse model of JEB. However, the adverse effects can be counteracted by the use of Losartan, an EB-anti-fibrotic drug.
Article
Genetics & Heredity
Daniele Castiglia, Paola Fortugno, Angelo Giuseppe Condorelli, Sabina Barresi, Naomi De Luca, Simone Pizzi, Iria Neri, Claudio Graziano, Diletta Trojan, Diego Ponzin, Sabrina Rossi, Giovanna Zambruno, Marco Tartaglia
Summary: Junctional epidermolysis bullosa (JEB) is a skin fragility disorder with clinical and genetic heterogeneity, commonly caused by mutations in genes encoding laminin-332. A novel JEB phenotype characterized by skin fragility resolution in infancy but persistent ocular involvement was identified, with biallelic LAMB3 mutations being the molecular basis. Human amniotic membrane (AM) eyedrop preparation was found effective for treating corneal lesions, restoring keratinocyte adhesion and resulting in long-lasting remission of ocular manifestations in JEB patients.
Article
Biochemistry & Molecular Biology
Janine Zwicklhuber, Thomas Kocher, Bernadette Liemberger, Stefan Hainzl, Johannes Bischof, Dirk Strunk, Anna M. Raninger, Iris Gratz, Verena Wally, Christina Guttmann-Gruber, Josefina Pinon Hofbauer, Johann W. Bauer, Ulrich Koller
Summary: In this study, a cell line suitable for gene expression studies of the JEB-associated COL17A1 gene was developed using the CRISPR/Cas9 system. The accurate expression and localization of the GFP-C17 fusion protein were confirmed. Repairing a JEB-associated frameshift mutation restored the expression and localization of the fusion protein. This fluorescence-based JEB cell line has the potential to be used for personalized gene editing and applications in vitro and in animal models in vivo.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Dermatology
Daniel Mosallaei, Michelle Hao, Richard J. Antaya, Brandon Levian, Andrew Kwong, Jon Cogan, Claire Hamilton, Agnes Schwieger-Briel, Calvin Tan, Xin Tang, David T. Woodley, Mei Chen
Summary: This study evaluated the safety and efficacy of intravenous gentamicin readthrough therapy in JEB patients. The results showed that gentamicin treatment induced readthrough of nonsense variants, restored functional laminin 332 expression, and promoted wound healing and closure in a 3-month period.
Article
Dermatology
Laura Trefzer, Agnes Schwieger-Briel, Alexander Nystroem, Gregor Conradt, Martin Pohl, Arkadiusz Miernik, Cristina Has
Summary: This study provides valuable insights into the kidney-urinary tract manifestations in patients with intermediate junctional epidermolysis bullosa (JEB), highlighting the importance of diagnosing and managing these complications effectively.
Review
Biochemistry & Molecular Biology
Nadezhda A. Evtushenko, Arkadii K. Beilin, Anastasiya Kosykh, Ekaterina A. Vorotelyak, Nadya G. Gurskaya
Summary: Epidermolysis bullosa simplex (EBS) is a group of genetic diseases caused by mutations in keratins, leading to changes in cellular pathology such as fragility of the intermediate filament network and basal layer cytolysis. Mutations in keratins can affect cellular signaling, cause abnormal cell migration, and trigger inflammatory responses.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Michael Ablinger, Thomas Lettner, Nicole Friedl, Hannah Potocki, Theresa Palmetzhofer, Ulrich Koller, Julia Illmer, Bernadette Liemberger, Stefan Hainzl, Alfred Klausegger, Manuela Reisenberger, Jo Lambert, Mireille Van Gele, Eline Desmet, Els Van Maelsaeke, Monika Wimmer, Roland Zauner, Johann W. Bauer, Verena Wally
Summary: Intermediate junctional epidermolysis bullosa caused by mutations in the COL17A1 gene is a rare disease with heterogeneous mutations, making therapy development challenging. However, the use of AON to induce exon skipping shows promise as a personalized treatment approach for this condition.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Genetics & Heredity
Laura De Rosa, Elena Enzo, Giulia Zardi, Christine Bodemer, Cristina Magnoni, Holm Schneider, Michele De Luca
Summary: Epidermolysis bullosa (EB) is a group of genetic diseases characterized by skin fragility and blisters, for which there is no definitive therapy. A study aims at using ex vivo gene therapy for the treatment of LAMB3-related junctional EB (JEB) by transplanting a graft of cultured transgenic keratinocytes and epidermal stem cells. The clinical trial will assess the efficacy, safety, and long-term outcomes of this combined cell and gene therapy approach.
FRONTIERS IN GENETICS
(2021)
Article
Multidisciplinary Sciences
Thomas C. Sproule, Vivek P. Philip, Nabig Chaudhry, Derry Roopenian, John Sundberg
Summary: Epidermolysis Bullosa (EB) is a rare genetic disorder that causes skin blistering and erosions after minor trauma. The severity and clinical presentations of EB can vary greatly, indicating the presence of genetic modifiers. A mouse model of non-Herlitz junctional EB (JEB-nH) showed that genetic modifiers, including the gene Col17a1, can significantly contribute to the phenotypic variability of EB. This study identified six additional Quantitative Trait Loci (QTL) that modify the disease in the mouse model, including known EB-related genes and genes related to modifier pathways. These findings expand our understanding of genetic modifiers of EB and potential therapeutic approaches.
Article
Dermatology
Matthew J. Davis, Gokul Srinivasan, Rachael Chacko, Sophie Chen, Anish Suvarna, Louis J. Vaickus, Veronica C. Torres, Sassan Hodge, Eunice Y. Chen, Sarah Preum, Kimberley S. Samkoe, Brock C. Christensen, Matthew R. Leboeuf, Joshua J. Levy
Summary: The development and application of AI algorithms are of great significance for the removal of cSCC, as they can improve operational efficiency and accuracy, especially for moderately and poorly differentiated tumors/ neoplasms. Further improvement is needed to maintain sensitivity to surrounding tissue and determine anatomical positioning.
EXPERIMENTAL DERMATOLOGY
(2024)
Article
Dermatology
Lingjing Chen, Qing Yu, Feiying Guo, Xuewen Wang, Zhenying Cai, Qiang Zhou
Summary: This study investigated the role and mechanisms of NTS in stress-induced hair growth inhibition. The results demonstrated that NTS effectively counteracted hair growth inhibition caused by stress and regulated the expression of multiple genes related to hair growth at the transcriptional level.
EXPERIMENTAL DERMATOLOGY
(2024)