title: Novel and recurrent mutations in keratin KRT5 and KRT14 genes in epidermolysis bullosa simplex: implications for disease phenotype and keratin filament assembly.
abstract: Epidermolysis bullosa simplex (EBS) is a group of autosomal dominant genetic skin disorders caused by mutations of the keratin genes KRT5 and KRT14. It is characterised by lysis of basal keratinocytes leading to the development of intraepidermal blisters upon minor mechanical trauma. We investigated 27 EBS patients and families of mainly German origin by sequence analysis of the entire coding sequences of KRT5 and KRT14 and identified 12 novel and seven previously reported mutations within the KRT5 and KRT14 genes. The study discusses possible implications of the novel mutations on protein structure, keratin intermediate filament (KIF) formation and the corresponding phenotype, and summarises the spectrum of mutations reported so far in EBS. Detailed knowledge of the spectrum of EBS mutations and their genotype-phenotype correlation is essential for accurate genetic counselling and prenatal diagnosis.
authors.affiliation: Department of Dermatology, University of Cologne, Cologne, Germany. felix.mueller@uni-koeln.de
authors.forename: Felix B
authors.initials: FB
authors.lastname: Müller
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Küster
authors.forename: Kerstin
authors.initials: K
authors.lastname: Wodecki
authors.forename: Hiram
authors.initials: H
authors.lastname: Almeida
authors.forename: Leena
authors.initials: L
authors.lastname: Bruckner-Tuderman
authors.forename: Thomas
authors.initials: T
authors.lastname: Krieg
authors.forename: Bernhard P
authors.initials: BP
authors.lastname: Korge
authors.forename: Meral J
authors.initials: MJ
authors.lastname: Arin
mesh_terms: D004252:DNA Mutational Analysis; D016110:Epidermolysis Bullosa Simplex / Q000175:diagnosis* / Q000235:genetics; D005817:Genetic Counseling; D005858:Germany / Q000208:ethnology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D053547:Keratin-14; D053555:Keratin-5; D007633:Keratins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D017434:Protein Structure, Tertiary
chemical_list: C507540:KRT14 protein, human; C503940:KRT5 protein, human; D053547:Keratin-14; D053555:Keratin-5; D007633:Keratins