title: Novel KRT14 mutation causing epidermolysis bullosa simplex with variable phenotype.
abstract: About 75% of cases of epidermolysis bullosa simplex result from mutations in KRT5 and KRT14 genes. Here, we report a family with a novel heterozygous missense mutation p.Leu418Gln in the KRT14 gene causing EBS of phenotype varying from EBS-loc to EBS-gen intermed. To the best of our knowledge, the family reported by us is the largest one in which two different phenotypes can be distinguished. The molecular dynamics simulations show that p.Leu418Gln mutation results in clear disruption of intermolecular π-stacking between KRT14:Tyr415 and KRT5:Tyr470, which in turn may affect putative phosphorylation site at KRT14:Thr414. This study further supports the importance of the EIATYR/KLLEGE motif in maintaining structural stability of KRT14:KRT5 heterodimer and indicates that physical properties of introduced amino acid can modulate the disease severity. The results obtained indicate further need of genotype-phenotype studies in EBS. In conclusion, genotype-based prognosis should be given to patients with caution.
authors: Department of Dermatology, Sexually Transmitted Diseases and Immunodermatology, Nicolaus Copernicus University, Bydgoszcz, Poland.
authors: Marek
authors: M
authors: Jankowski
authors: Katarzyna
authors: K
authors: Wertheim-Tysarowska
authors: Rafal
authors: R
authors: Jakubowski
authors: Justyna
authors: J
authors: Sota
authors: Wieslaw
authors: W
authors: Nowak
authors: Rafal
authors: R
authors: Czajkowski
mesh_terms: D019943:Amino Acid Substitution; D016110:Epidermolysis Bullosa Simplex / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006579:Heterozygote; D006801:Humans; D053547:Keratin-14 / Q000737:chemistry / Q000235:genetics*; D053555:Keratin-5 / Q000737:chemistry; D008297:Male; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D050505:Mutant Proteins / Q000737:chemistry / Q000235:genetics; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D054730:Protein Interaction Domains and Motifs; D055550:Protein Stability
chemical_list: C507540:KRT14 protein, human; C503940:KRT5 protein, human; D053547:Keratin-14; D053555:Keratin-5; D050505:Mutant Proteins
keywords: G138E; KRT14; epidermolysis bullosa simplex; hyperkeratosis; molecular dynamics