Epidermolysis bullosa simplex–generalized severe type due to keratin 5 p.Glu477Lys mutation: Genotype-phenotype correlation and in silico modeling analysis

Leah Lalor, Matthias Titeux, Francis Palisson, Ignacia Fuentes, María J. Yubero, Kaisa Tasanen, Laura Huilaja, Cristina Has, Gianluca Tadini, Anita N. Haggstrom, Alain Hovnanian, Anne W. Lucky

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)132-138
Number of pages7
JournalPediatric Dermatology
Volume36
Issue number1
DOIs
StatePublished - Jan 1 2019

Keywords

  • epidermolysis bullosa
  • genetic diseases/mechanisms
  • genodermatoses

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Dermatology

Fingerprint Dive into the research topics of 'Epidermolysis bullosa simplex–generalized severe type due to keratin 5 p.Glu477Lys mutation: Genotype-phenotype correlation and in silico modeling analysis'. Together they form a unique fingerprint.

Cite this