title: Epidermolysis bullosa simplex in Israel: clinical and genetic features.
abstract: BACKGROUND
  Epidermolysis bullosa simplex (EBS) is the most common form of epidermolysis bullosa. The disease is characterized by intraepidermal blistering due in most cases to mutations in cytokeratin genes 5 (K5) or 14 (K14). Extensive studies in the United States and Europe have shown that EBS is almost always inherited in an autosomal dominant fashion.
  
  
  OBJECTIVE
  To assess the possibility that the molecular features of EBS may differ according to the type of population studied.
  
  
  METHODS
  We assessed 10 Israeli families diagnosed as having EBS and compared their clinical and genetic features with previous observations. Affected individuals underwent complete clinical evaluation. DNA from all family members was assessed for mutations in K5 or K14 using polymerase chain reaction amplification, direct sequencing, and subsequent mutation verification. In addition, specific cases were genotyped using a panel of microsatellite markers spanning the K14 locus.
  
  
  RESULTS
  Eight distinct pathogenic mutations in K5 (3 mutations) and K14 (5 mutations) were identified. Six of these mutations are novel. The mutations included 2 nonsense mutations and 6 missense mutations. A third of the affected families inherited EBS in a recessive fashion, in contrast with previous observations in Europe and the United States. In addition, we identified a unique case that resulted from compound heterozygosity for a missense and a nonsense mutation in K14. Homozygous nonsense mutations were strongly associated with a severe phenotype.
  
  
  CONCLUSIONS
  The present study demonstrates a unique mutation spectrum and a strikingly different pattern of inheritance for EBS in a series of Israeli families compared with families of European or US extraction.
authors.affiliation: The Gunther Kahn Department of Dermatology and Laboratory of Molecular Dermatology, Rambam Medical Center, Haifa, Israel.
authors.forename: Dan
authors.initials: D
authors.lastname: Ciubotaru
authors.forename: Reuven
authors.initials: R
authors.lastname: Bergman
authors.forename: David
authors.initials: D
authors.lastname: Baty
authors.forename: Margarita
authors.initials: M
authors.lastname: Indelman
authors.forename: Ellen
authors.initials: E
authors.lastname: Pfendner
authors.forename: Danny
authors.initials: D
authors.lastname: Petronius
authors.forename: Hannah
authors.initials: H
authors.lastname: Moualem
authors.forename: Moien
authors.initials: M
authors.lastname: Kanaan
authors.forename: Danny
authors.initials: D
authors.lastname: Ben Amitai
authors.forename: W H Irwin
authors.initials: WH
authors.lastname: McLean
authors.forename: Jouni
authors.initials: J
authors.lastname: Uitto
authors.forename: Eli
authors.initials: E
authors.lastname: Sprecher
mesh_terms: D018389:Codon, Nonsense; D016110:Epidermolysis Bullosa Simplex / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D007557:Israel; D053547:Keratin-14; D053555:Keratin-5; D007633:Keratins / Q000235:genetics; D008297:Male; D018895:Microsatellite Repeats; D009154:Mutation; D020125:Mutation, Missense; D016133:Polymerase Chain Reaction
chemical_list: D018389:Codon, Nonsense; C507540:KRT14 protein, human; C503940:KRT5 protein, human; D053547:Keratin-14; D053555:Keratin-5; D007633:Keratins