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
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
Biochemistry & Molecular Biology
Nailah Harvey, Leila Youssefian, Amir Hossein Saeidian, Hassan Vahidnezhad, Jouni Uitto
Summary: Epidermolysis bullosa (EB) is a phenotypically and genetically heterogeneous disorder caused by mutations in genes encoding structural proteins that reinforce skin integrity. Breakdowns in these proteins lead to the disruption of skin adhesion mechanisms. Despite clinical and histopathological confirmation, there are still many genetically unsolved cases of EB. Recent advancements have implicated non-structural proteins in the pathophysiology of EB.
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)
Review
Medicine, General & Internal
Monica-Cristina Panzaru, Lavinia Caba, Laura Florea, Elena Emanuela Braha, Eusebiu Vlad Gorduza
Summary: Epidermolysis bullosa is a rare genetic disorder characterized by fragility of the mucocutaneous tissue and blister formation. It can be classified into four major types based on the ultrastructural level of tissue cleavage. Mutations in genes encoding proteins involved in hemidesmosomes and focal adhesion complex are responsible for this disease. Some cases may also have extracutaneous manifestations that can be fatal. This review focuses on the heterogeneity and genotype-phenotype correlation in epidermolysis bullosa.
Editorial Material
Medicine, General & Internal
Aimee S. S. Payne
Summary: This article describes a new trial of gene therapy for dystrophic epidermolysis bullosa, which is notable for its topical application for treating the skin disorder.
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Cameron Meyer-Mueller, Mark J. Osborn, Jakub Tolar, Christina Boull, Christen L. Ebens
Summary: Epidermolysis bullosa (EB) is a group of genetic blistering diseases characterized by fragile skin. A recent study suggests that revertant mosaicism (RM), a phenomenon that corrects disease-causing mutations, could be a potential therapy for EB. RM cells provide a powerful autologous platform for therapy, avoiding the risks associated with gene therapy/editing. However, more research is needed to ensure the genomic integrity and long-term functionality of RM-derived cells.
Letter
Dermatology
Fuying Chen, Dan Deng, Chaolan Pan, Zhirong Yao, Yan Gu, Ming Li
Summary: This study reports for the first time the proportion of low-level mosaicism in clinically unaffected parents, whose children were previously regarded as sporadic EBS cases.
BRITISH JOURNAL OF DERMATOLOGY
(2022)
Article
Dermatology
Kata P. Szilveszter, Simon Vikar, Adam Horvath, Zsuzsanna Helyes, Miklos Sardy, Attila Mocsai
Summary: Phospholipase C gamma 2 (PLC gamma 2) plays a critical role in the pathogenesis of inflammatory epidermolysis bullosa acquisita by regulating the tissue infiltration of immune cells and the release of proinflammatory mediators.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2022)
Article
Dermatology
Lauren Banner, Alexa Cohen, Lauren McGrath, Neda Nikbakht, Andrew P. South
Summary: We report a novel homozygous KRT14 mutation in a patient with a mild form of epidermolysis bullosa simplex (EBS). The patient has loss of function in both alleles of the KRT14 gene. This is the 16th reported mutation of recessive EBS in KRT14.
CLINICAL AND EXPERIMENTAL DERMATOLOGY
(2023)
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
Biotechnology & Applied Microbiology
Jose Bonafont, Angeles Mencia, Esteban Chacon-Solano, Wai Srifa, Sriram Vaidyanathan, Rosa Romano, Marta Garcia, Rosario Hervas-Salcedo, Laura Ugalde, Blanca Duarte, Matthew H. Porteus, Marcela Del Rio, Fernando Larcher, Rodolfo Murillas
Summary: This study presents a gene-editing approach using CRISPR-Cas9 system to achieve gene correction in different cell types, showing therapeutic potential for RDEB.
Article
Cell Biology
Laura De Rosa, Elena Enzo, Michele Palamenghi, Laura Sercia, Michele De Luca
Summary: Epidermolysis bullosa (EB) is a genetic skin disease with diverse phenotypes, ranging from severe to mild forms. Recent advancements in pharmacology and biology have led to the development of new therapeutic strategies for controlling inflammation, promoting wound healing, and targeting epidermal stem cells for tissue regeneration. However, understanding the genetic variants and other factors that influence the correlation between genotype and phenotype in EB is crucial for effective treatment.
COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY
(2023)
Review
Immunology
Sabrina Patzelt, Enno Schmidt
Summary: Laminin 332 is a crucial protein for the structural integrity of the skin and mucosal tissues. Mutations in its encoding genes can lead to junctional epidermolysis bullosa. Autoimmunity against laminin 332 is observed in mucous membrane pemphigoid, where antibodies target the BMZ. Studies have also found an association between anti-laminin 332 MMP and malignancies.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Dermatology
Yueqian Yu, Zhenzhen Wang, Zihao Mi, Lele Sun, Xi'an Fu, Gongqi Yu, Zheng Pang, Hong Liu, Furen Zhang
Summary: This study identified 52 pathogenic mutations in a large cohort of Chinese patients with epidermolysis bullosa using whole-exome sequencing, revealing the relationship between different subtypes and pathogenic genes. The results support whole-exome sequencing as a promising tool in the genetic diagnosis of epidermolysis bullosa.
ACTA DERMATO-VENEREOLOGICA
(2021)
