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
Dermatology
Fuying Chen, Ruoqu Wei, Dan Deng, Xue Zhang, Yu Cao, Chaolan Pan, Yumeng Wang, Qiaoyu Cao, Jianbo Wang, Ming Zeng, Linting Huang, Yan Gu, Zhirong Yao, Ming Li
Summary: This study analyzed the genotype-phenotype correlation in Chinese individuals with EB and identified rare phenotypes and complex genotypes.
JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY
(2023)
Article
Multidisciplinary Sciences
Ana C. Laly, Kristina Sliogeryte, Oscar J. Pundel, Rosie Ross, Michael C. Keeling, Deepa Avisetti, Ahmad Waseem, Nuria Gavara, John T. Connelly
Summary: The keratin cytoskeleton plays a critical role in sensing matrix rigidity, with keratinocytes adapting to increased stiffness by forming a rigid interconnected network and boosting cell stiffness. Mutations disrupting keratin stability hinder the normal mechanical response and impair mechanotransduction. Depletion of cytolinker proteins, however, enhances mechanoresponsiveness and up-regulates lamin A/C.
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
Fuying Chen, Lei Yao, Xue Zhang, Yan Gu, Hong Yu, Zhirong Yao, Jia Zhang, Ming Li
Summary: This study identified a novel homozygous c.1474T>C mutation in the KRT5 gene causing a localized recessive form of EBS. The mutation led to structural changes in keratin 5 and altered signaling pathways, with an upregulation of desmoglein 1. The findings suggest that keratin 5 plays a role in maintaining desmoglein 1 levels through the MAPK signaling pathway.
FRONTIERS IN GENETICS
(2021)
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.
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.
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.
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
Dermatology
Xin Jiang, Yingyu Zhu, Huihui Sun, Feng Gu
Summary: This study identified a novel genetic mutation in a Chinese family with localized EBS, expanding the mutational spectrum of EBS and providing valuable insights for prenatal screening, gene diagnosis, and gene therapy for localized EBS.
ANNALS OF DERMATOLOGY
(2021)
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)
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.
