{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T09:32:42Z","timestamp":1774085562075,"version":"3.50.1"},"reference-count":43,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,12,4]],"date-time":"2018-12-04T00:00:00Z","timestamp":1543881600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002850","name":"Fondo Nacional de Desarrollo Cient\u00edfico y Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["11140440"],"award-info":[{"award-number":["11140440"]}],"id":[{"id":"10.13039\/501100002850","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Dermatology"],"published-print":{"date-parts":[[2019,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background\/Objectives<\/jats:title><jats:p>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\u2010phenotype 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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\u2010keratin 14 coil 2B complex using <jats:styled-content style=\"fixed-case\">CCB<\/jats:styled-content>uilder and rendered with Pymol (Schrodinger, LLC, New York, NY).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Early recognition of the features of this genotype will improve care. In silico analysis of mutated keratin structures provides useful insights into structural instability.<\/jats:p><\/jats:sec>","DOI":"10.1111\/pde.13722","type":"journal-article","created":{"date-parts":[[2018,12,5]],"date-time":"2018-12-05T06:57:03Z","timestamp":1543993023000},"page":"132-138","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Epidermolysis bullosa simplex\u2013generalized severe type due to keratin 5 p.Glu477Lys mutation: Genotype\u2010phenotype correlation and in silico modeling analysis"],"prefix":"10.1111","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1017-8649","authenticated-orcid":false,"given":"Leah","family":"Lalor","sequence":"first","affiliation":[{"name":"Division of Pediatric Dermatology MCW Department of Dermatology Milwaukee Wisconsin"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthias","family":"Titeux","sequence":"additional","affiliation":[{"name":"Laboratory of Genetic Skin Diseases Inserm UMR1163 Imagine Institute Paris France"},{"name":"University Paris Descartes \u2010 Sorbonne Paris Cite Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francis","family":"Palisson","sequence":"additional","affiliation":[{"name":"Fundacion DEBRA Chile Santiago Chile"},{"name":"Facultad de Medicina Clinica Alemana Universidad del Desarrollo Santiago Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ignacia","family":"Fuentes","sequence":"additional","affiliation":[{"name":"Fundacion DEBRA Chile Santiago Chile"},{"name":"Centro de Genetica y Genomica Facultad de Medicina Clinica Alemana Universidad del Desarrollo Santiago Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda 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Freiburg Freiburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1164-2802","authenticated-orcid":false,"given":"Gianluca","family":"Tadini","sequence":"additional","affiliation":[{"name":"Pediatric Dermatology Fondazione IRCC Ca'Granda \u2010 Ospedale Maggiore Policlinico di Milano Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9088-8079","authenticated-orcid":false,"given":"Anita N.","family":"Haggstrom","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Pediatrics Indiana University Indianapolis Indiana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alain","family":"Hovnanian","sequence":"additional","affiliation":[{"name":"Laboratory of Genetic Skin Diseases Inserm UMR1163 Imagine Institute Paris France"},{"name":"University Paris Descartes \u2010 Sorbonne Paris Cite Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6115-7584","authenticated-orcid":false,"given":"Anne W.","family":"Lucky","sequence":"additional","affiliation":[{"name":"Epidermolysis Bullosa Center Cincinnati Children's Hospital Medical Center Cincinnati 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