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Epidermolysis bullosa simplex–generalized severe type due to keratin 5 p.Glu477Lys mutation: Genotype‐phenotype correlation and in silico modeling analysis
- Source :
- Pediatric Dermatology. 36:132-138
- Publication Year :
- 2018
- Publisher :
- Wiley, 2018.
-
Abstract
- Background/objectives Epidermolysis bullosa is a group of diseases caused by mutations in skin structural proteins. Availability of genetic sequencing makes identification of causative mutations easier, and genotype-phenotype description and correlation are important. We describe six patients with a keratin 5 mutation resulting in a glutamic acid to lysine substitution at position 477 (p.Glu477Lys) who have a distinctive, severe and sometimes fatal phenotype. We also perform in silico modeling to show protein structural changes resulting in instability. Methods In this case series, we collected clinical data from six patients with this mutation identified from their national or local epidermolysis bullosa databases. We performed in silico modeling of the keratin 5-keratin 14 coil 2B complex using CCBuilder and rendered with Pymol (Schrodinger, LLC, New York, NY). Results Features include aplasia cutis congenita, generalized blistering, palmoplantar keratoderma, onychodystrophy, airway and developmental abnormalities, and a distinctive reticulated skin pattern. Our in silico model of the keratin 5 p.Glu477Lys mutation predicts conformational change and modification of the surface charge of the keratin heterodimer, severely impairing filament stability. Conclusions Early recognition of the features of this genotype will improve care. In silico analysis of mutated keratin structures provides useful insights into structural instability.
- Subjects :
- Male
Databases, Factual
Genotype
In silico
Dermatology
030207 dermatology & venereal diseases
03 medical and health sciences
Epidermolysis bullosa simplex
0302 clinical medicine
Keratin
Humans
Medicine
Computer Simulation
Child
skin and connective tissue diseases
Genetic Association Studies
Skin
chemistry.chemical_classification
Genetics
integumentary system
business.industry
Infant, Newborn
medicine.disease
Keratin 5
Phenotype
Palmoplantar keratoderma
chemistry
Child, Preschool
Epidermolysis Bullosa Simplex
030220 oncology & carcinogenesis
Mutation
Pediatrics, Perinatology and Child Health
Mutation (genetic algorithm)
Keratin-5
Female
Epidermolysis bullosa
business
Subjects
Details
- ISSN :
- 15251470 and 07368046
- Volume :
- 36
- Database :
- OpenAIRE
- Journal :
- Pediatric Dermatology
- Accession number :
- edsair.doi.dedup.....679c5316235f70345da9a21526383957
- Full Text :
- https://doi.org/10.1111/pde.13722