Epidermolysis bullosa simplex-generalized severe due to p.Glu477Lys mutation in keratin 5: a genotype-phenotype correlation with in silico modeling analysis

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dc.contributor.authorLalor, Leah
dc.contributor.authorTiteux, Matthias
dc.contributor.authorPalisson, Francis
dc.contributor.authorFuentes, Ignacia
dc.contributor.authorYubero, María
dc.contributor.authorTasanen, Kaisa
dc.contributor.authorHuilaja, Laura
dc.contributor.authorHas, Cristina
dc.contributor.authorTadini, Gianluca
dc.contributor.authorHaggstrom, Anita N.
dc.contributor.authorHovnanian, Alain
dc.contributor.authorLucky, Anne W.
dc.date.accessioned2020-04-02T15:52:03Z
dc.date.available2020-04-02T15:52:03Z
dc.date.issued2019
dc.description.abstractBackground/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.
dc.description.versionVersión Publicada
dc.format.extent19 p.
dc.identifier.citationLalor L, Titeux M, Palisson F, Fuentes I, Yubero MJ, Tasanen K, Huilaja L, Has C, Tadini G, Haggstrom AN, Hovnanian A, Lucky AW. Epidermolysis bullosa simplex-generalized severe type due to keratin 5 p.Glu477Lys mutation: Genotype-phenotype correlation and in silico modeling analysis. Pediatr Dermatol. 2019 Jan;36(1):132-138. doi: 10.1111/pde.13722.
dc.identifier.urihttp://hdl.handle.net/11447/3202
dc.identifier.urihttps://doi.org/10.1111/pde.13722
dc.language.isoen
dc.sourcePediatric Dermatology
dc.subjectEpidermolysis bullosa
dc.subjectGenetic diseases/mechanisms
dc.subjectGenodermatoses
dc.titleEpidermolysis bullosa simplex-generalized severe due to p.Glu477Lys mutation in keratin 5: a genotype-phenotype correlation with in silico modeling analysis
dc.typeArticle

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