Analysis of KRT5 and KRT14 gene mutations and mode of inheritance in Iranian patients with clinical suspicion of Epidermolysis bullosa simplex

Abstract

Background: Epidermolysis bullosa simplex is a hereditary skin disorder caused by mutations in several genes such as KRT5 and KRT14. Skin fragility in basal keratinocytes presence regions led to the cytolysis of epidermis and blistering. Aim of this study was to detect the molecular defects in KRT5 and KRT14 genes hot spots in patients with clinical suspicion of EBS and investigation of their probable genotype-phenotype correlations. Methods: Exons 1 and 6-7 of KRT5 and exons 1 and 4-7 of KRT14 amplification and mutation detection were performed by polymerase chain reaction and Sanger sequencing, respectively. Novel variants pathogenicity evaluated by bioinformatics tools. Results: Nine important variants detected in seven different patients within 6 Iranian families affected by Epidermolysis bullosa simplex, of which four variants were novel. Three patients had a mottled pigmentation phenotype G96D (p. Gly96Asp) and F97I (p. Phe97Ile) in KRT5. One of them showed a Dowling-Meara phenotype A417P (p. Ala417Pro) and E477D (p. Glu477Asp) in KRT5 and another had a Koebner type phenotype R397I (p. Arg397Ile) and Q444* (p. Gln444Ter) in KRT5. A novel variant G92E (p. Gly92Glu) in KRT5 in a double heterozygous state with a challenging variant A413T (p. Ala413Thr) in KRT14 identified in one patient with Koebner type phenotype. Also, a previously reported mutation I377T (p. Ile377Thr) in KRT14 gene identified in this study. Conclusion: The results of molecular data analysis showed that the most severe phenotypes were associated with mutations in highly conserved regions. In some cases, different inheritance modes were observed. © Iran University of Medical Sciences