title: Novel sporadic and recurrent mutations in KRT5 and KRT14 genes in Polish epidermolysis bullosa simplex patients: further insights into epidemiology and genotype-phenotype correlation.
abstract: Epidermolysis bullosa simplex (EBS) is a hereditary genodermatosis characterised by trauma-induced intraepidermal blistering of the skin. EBS is mostly caused by mutations in the KRT5 and KRT14 genes. Disease severity partially depends on the affected keratin type and may be modulated by mutation type and location. The aim of our study was to identify the molecular defects in KRT5 and KRT14 in a cohort of 46 Polish and one Belarusian probands with clinical suspicion of EBS and to determine the genotype-phenotype correlation. The group of 47 patients with clinical recognition of EBS was enrolled in the study. We analysed all coding exons of KRT5 and KRT14 using Sanger sequencing. The pathogenic status of novel variants was evaluated using bioinformatical tools, control group analysis (DNA from 100 healthy population-matched subjects) and probands' parents testing. We identified mutations in 80 % of patients and found 29 different mutations, 11 of which were novel and six were found in more than one family. All novel mutations were ascertained as pathogenic. In the majority of cases, the most severe genotype was associated with mutations in highly conserved regions. In some cases, different inheritance mode and clinical significance, than previously reported by others, was observed. We report 11 novel variants and show novel genotype-phenotype correlations. Our data give further insight into the natural history of EBS molecular pathology, epidemiology and mutation origin.
authors.affiliation: Department of Medical Genetics, Institute of Mother and Child, Kasprzaka 17a, 01211, Warsaw, Poland. katarzyna.wertheim@imid.med.pl.
authors.forename: K
authors.initials: K
authors.lastname: Wertheim-Tysarowska
authors.affiliation: Department of Histology and Embryology, Center of Biostructure Research, Medical University of Warsaw, Chalubinskiego 5, 02004, Warsaw, Poland.|Department of Genetics, World Hearing Center, Institute of Physiology and Pathology of Hearing, Warsaw, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Ołdak
authors.affiliation: Department of Medical Genetics, Institute of Mother and Child, Kasprzaka 17a, 01211, Warsaw, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Giza
authors.affiliation: Department of Medical Genetics, Institute of Mother and Child, Kasprzaka 17a, 01211, Warsaw, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Kutkowska-Kaźmierczak
authors.affiliation: Department of Medical Genetics, Institute of Mother and Child, Kasprzaka 17a, 01211, Warsaw, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Sota
authors.affiliation: Department of Histology and Embryology, Center of Biostructure Research, Medical University of Warsaw, Chalubinskiego 5, 02004, Warsaw, Poland.
authors.forename: D
authors.initials: D
authors.lastname: Przybylska
authors.affiliation: Department of Dermatology and Immunodermatology, Medical University of Warsaw, Chalubinskiego 5, 02004, Warsaw, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Woźniak
authors.affiliation: Department of Medical Genetics, Institute of Mother and Child, Kasprzaka 17a, 01211, Warsaw, Poland.
authors.forename: D
authors.initials: D
authors.lastname: Śniegórska
authors.affiliation: Department of Medical Genetics, Institute of Mother and Child, Kasprzaka 17a, 01211, Warsaw, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Niepokój
authors.affiliation: Department of Medical Genetics, Institute of Mother and Child, Kasprzaka 17a, 01211, Warsaw, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Sobczyńska-Tomaszewska
authors.affiliation: Department of Medical Genetics, Institute of Mother and Child, Kasprzaka 17a, 01211, Warsaw, Poland.
authors.forename: A M
authors.initials: AM
authors.lastname: Rygiel
authors.affiliation: Department of Genetics, Medical University of Warsaw, Pawińskiego 5a, 02004, Warsaw, Poland.
authors.forename: R
authors.initials: R
authors.lastname: Płoski
authors.affiliation: Department of Medical Genetics, Institute of Mother and Child, Kasprzaka 17a, 01211, Warsaw, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Bal
authors.affiliation: Department of Dermatology and Immunodermatology, Medical University of Warsaw, Chalubinskiego 5, 02004, Warsaw, Poland.
authors.forename: C
authors.initials: C
authors.lastname: Kowalewski
mesh_terms: D004252:DNA Mutational Analysis; D016110:Epidermolysis Bullosa Simplex / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D060005:Genotyping Techniques; D006801:Humans; D053547:Keratin-14 / Q000235:genetics*; D053555:Keratin-5 / Q000235:genetics*; D008297:Male; D009154:Mutation; D010375:Pedigree; D011044:Poland
chemical_list: C507540:KRT14 protein, human; C503940:KRT5 protein, human; D053547:Keratin-14; D053555:Keratin-5
keywords: Epidermolysis bullosa simplex (EBS); KRT14; KRT5