ArticleProceedings of the National Academy of Sciences of the United States of America1993
Disease severity correlates with position of keratin point mutations in patients with epidermolysis bullosa simplex.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1993. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 123 citations in OpenAlex.
- KRT5 missense variant in a Cardigan Welsh Corgi with epidermolysis bullosa simplex.Animal genetics · 2022Article
- Detrimental Effects of IFN-γ on an Epidermolysis Bullosa Simplex Cell Model and Protection by a Humanized Anti-IFN-γ Monoclonal Antibody.JID innovations : skin science from molecules to population health · 2022Article
- Structure-Function Analyses of a Keratin Heterotypic Complex Identify Specific Keratin Regions Involved in Intermediate Filament Assembly.Structure (London, England : 1993) · 2020Article
- Known and novel mutations responsible for epidermolysis bullosa simplex cases in a Chinese population.Experimental and therapeutic medicine · 2019Article
- Traceless Targeting and Isolation of Gene-Edited Immortalized Keratinocytes from Epidermolysis Bullosa Simplex Patients.Molecular therapy. Methods & clinical development · 2017Article
- Analysis of 589,306 genomes identifies individuals resilient to severe Mendelian childhood diseases.Nature biotechnology · 2016Article
- Whole-transcriptome gene expression profiling in an epidermolysis bullosa simplex Dowling-Meara model keratinocyte cell line uncovered novel, potential therapeutic targets and affected pathways.BMC research notes · 2015Article
- Complementary roles of specific cysteines in keratin 14 toward the assembly, organization, and dynamics of intermediate filaments in skin keratinocytes.The Journal of biological chemistry · 2015Article
- Emerging roles of sumoylation in the regulation of actin, microtubules, intermediate filaments, and septins.Cytoskeleton (Hoboken, N.J.) · 2015Review
- Two desmin gene mutations associated with myofibrillar myopathies in Polish families.PloS one · 2014Article
- Defining keratin protein function in skin epithelia: epidermolysis bullosa simplex and its aftermath.The Journal of investigative dermatology · 2012Review
- Modeling the self-organization property of keratin intermediate filaments.Biophysical journal · 2010Article
- Epidermolysis bullosa simplex: a paradigm for disorders of tissue fragility.The Journal of clinical investigation · 2009Review
- Novel transglutaminase-1 mutations and genotype-phenotype investigations of 104 patients with autosomal recessive congenital ichthyosis in the USA.Journal of medical genetics · 2009Article
- Therapeutic siRNAs for dominant genetic skin disorders including pachyonychia congenita.Journal of dermatological science · 2008Review
- Reprogramming of keratin biosynthesis by sulforaphane restores skin integrity in epidermolysis bullosa simplex.Proceedings of the National Academy of Sciences of the United States of America · 2007Article
- Severe muscle disease-causing desmin mutations interfere with in vitro filament assembly at distinct stages.Proceedings of the National Academy of Sciences of the United States of America · 2005Article
- Defining the properties of the nonhelical tail domain in type II keratin 5: insight from a bullous disease-causing mutation.Molecular biology of the cell · 2005Article
- Characterization of structural changes in vimentin bearing an epidermolysis bullosa simplex-like mutation using site-directed spin labeling and electron paramagnetic resonance.The Journal of biological chemistry · 2005Article
- Functional improvement of mutant keratin cells on addition of desmin: an alternative approach to gene therapy for dominant diseases.Gene therapy · 2004Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Keratins are the major structural proteins of the epidermis. Recently, it was discovered that point mutations in the epidermal keratins can lead to the blistering skin diseases epidermolysis bullosa simplex (EBS) and epidermolytic hyperkeratosis (EH), involving epidermal cell fragility and rupture upon mechanical stress. In this study, we demonstrate a correlation between disease severity, location of point mutations within the keratin polypeptides, and degree to which these mutations perturb keratin filament structure. Interestingly, of the 11 EBS or EH mutations thus far identified, 6 affect a single highly evolutionarily conserved arginine residue, which, when mutated, markedly perturbs keratin filament structure and keratin network formation. This site also appears to be a hot spot for mutation by CpG methylation and deamination. In the four epidermal keratins, there are several other CpG dinucleotides that exist at codons within the highly conserved ends of the keratin rod. To elucidate why mutations at these sites have not been detected in severe cases of EBS, we engineered 7 of these C-->T transitions in K14 and tested their ability to perturb keratin network formation and keratin filament assembly in vitro. The effects of these mutants on keratin filament network formation were significantly less severe than the EBS/EH arginine mutation, suggesting that the high incidence of mutations of the residue in EBS and EH patients is a result of both a special sensitivity of filament structure to perturbations in this residue and its susceptibility to mutagenesis.
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