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Novel KRT 14 mutation causing epidermolysis bullosa simplex with variable phenotype
Author(s) -
Jankowski Marek,
WertheimTysarowska Katarzyna,
Jakubowski Rafal,
Sota Justyna,
Nowak Wieslaw,
Czajkowski Rafal
Publication year - 2014
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.12478
Subject(s) - epidermolysis bullosa simplex , missense mutation , phenotype , mutation , genotype , genetics , gene , genotype phenotype distinction , biology , medicine
About 75% of cases of epidermolysis bullosa simplex result from mutations in KRT 5 and KRT 14 genes. Here, we report a family with a novel heterozygous missense mutation p.Leu418Gln in the KRT 14 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 KRT 14:Tyr415 and KRT 5:Tyr470, which in turn may affect putative phosphorylation site at KRT 14:Thr414. This study further supports the importance of the EIATYR / KLLEGE motif in maintaining structural stability of KRT 14: KRT 5 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.