title: Clinical heterogeneity in recessive epidermolysis bullosa due to mutations in the keratin 14 gene, KRT14.
abstract: BACKGROUND
  Epidermolysis bullosa simplex (EBS), the most common subtype of EB, is usually inherited as an autosomal dominant trait caused by mutations in either the keratin 5 (KRT5) or keratin 14 (KRT14) genes. Recessive EBS (R-EBS) is extremely rare.
  
  
  METHODS
  We present the first Australian patient diagnosed with R-EBS, to our knowledge, and a comprehensive review of genotypes and phenotypes of R-EBS reported cases.
  
  
  RESULTS
  The female proband, of Turkish descent with consanguineous parentage, was referred to us at the age of 8 years. Clinically, she had a severe phenotype including generalized blisters, mucosal involvement and EB naevi. Immunofluorescence mapping and electron microscopy were consistent with a diagnosis of EBS. Staining for Keratin 14 (K14) was negative. The basal layer, however, reacted with monoclonal antibodies to keratins 6 (K6) and 16 (K16). Mutation screening from genomic DNA showed that the proband was homozygous for the truncation mutation Y204X in exon 3 of KRT14, and both unaffected parents were heterozygous for a single KRT14 Y204X mutation. The phenotype of our patient is reported in more detail and with longer follow-up than those of others published in the literature.
  
  
  CONCLUSIONS
  The proband's phenotype was severe as an infant but improved with age, suggesting that an alternative keratin is pairing with K5 in her skin to compensate for the loss of K14--a novel biological compensatory mechanism. It is interesting that K6 and K16 were expressed, as these are normally positive in hyperproliferative skin disorders.
authors: Department of Dermatology, St George Hospital, Sydney, New South Wales, Australia.
authors: E
authors: E
authors: Yiasemides
authors: N
authors: N
authors: Trisnowati
authors: J
authors: J
authors: Su
authors: N
authors: N
authors: Dang
authors: S
authors: S
authors: Klingberg
authors: P
authors: P
authors: Marr
authors: W
authors: W
authors: Melbourne
authors: K
authors: K
authors: Tran
authors: C W
authors: CW
authors: Chow
authors: D
authors: D
authors: Orchard
authors: G
authors: G
authors: Varigos
authors: D F
authors: DF
authors: Murrell
mesh_terms: D001315:Australia; D002648:Child; D003241:Consanguinity; D004820:Epidermolysis Bullosa / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D005260:Female; D005455:Fluorescent Antibody Technique; D017353:Gene Deletion; D005808:Genes, Recessive; D006720:Homozygote; D006801:Humans; D053547:Keratin-14 / Q000235:genetics*; D053536:Keratin-16 / Q000235:genetics; D053553:Keratin-6 / Q000235:genetics; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D012867:Skin / Q000648:ultrastructure; D014421:Turkey / Q000208:ethnology
chemical_list: D053547:Keratin-14; D053536:Keratin-16; D053553:Keratin-6