title: Novel and recurrent mutations in Keratin 5 and 14 in Korean patients with Epidermolysis bullosa simplex.
abstract: BACKGROUND
  Epidermolysis bullosa simplex (EBS) is a group of hereditary bullous disorders caused by mutations in the keratin genes KRT5 and KRT14. A significant genotype-phenotype correlation has been noted in previous studies of EBS.
  
  
  OBJECTIVE
  In order to identify additional EBS mutations and elucidate the genotype-phenotype correlations in Korean EBS patients, we performed the first large scale mutational analysis of EBS patients of Korean origin.
  
  
  METHODS
  We investigated fifteen Korean EBS patients by performing a sequence analysis of the entire coding sequences of KRT5 and KRT14.
  
  
  RESULTS
  We identified six novel mutations, four within KRT5 (p.V143F, p.R265P, p.C479X and p.Asn177del), and two within KRT14 (p.R125L and p.L401P). In all, 13 missense, 1 nonsense, and 1 small deletion mutation were found. Five mutations in Dowling-Meara type (K14-p.R125H, K14-p.R125L, K5-E477K, K5-p.C479X and K5-p.Asn177del) were located in the highly conserved ends of the alpha-helical rod domain, the helix initiation (HIP), or helix termination (HTP) peptides of KRT5 and KRT14. Further, seven and three mutations were identified in EBS-generalized type and EBS-localized type, respectively. The positions of the mutations in both subtypes were more widely distributed within the rod domains and in the L12 linker domains of both keratin genes.
  
  
  CONCLUSIONS
  This study should provide useful data and enhance our understanding of the EBS genotype-phenotype relationship. The genotype-phenotype correlation in Korean EBS patients was similar to previous studies performed in other ethnic groups. Lastly, our results confirmed that the mutational location in KRT5 or KRT14 is the most important factor in determining the phenotype severity.
authors.affiliation: Department of Dermatology and Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul 135-720, Republic of Korea.
authors.forename: Tae-Won
authors.initials: TW
authors.lastname: Kang
authors.forename: Jeong Seon
authors.initials: JS
authors.lastname: Lee
authors.forename: Song-Ee
authors.initials: SE
authors.lastname: Kim
authors.forename: Se-Woong
authors.initials: SW
authors.lastname: Oh
authors.forename: Soo-Chan
authors.initials: SC
authors.lastname: Kim
mesh_terms: D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics*; D018389:Codon, Nonsense; D016110:Epidermolysis Bullosa Simplex / Q000208:ethnology* / Q000235:genetics* / Q000473:pathology; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D053547:Keratin-14 / Q000235:genetics*; D053555:Keratin-5 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020125:Mutation, Missense; D010641:Phenotype; D017421:Sequence Analysis; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D018389:Codon, Nonsense; C507540:KRT14 protein, human; C503940:KRT5 protein, human; D053547:Keratin-14; D053555:Keratin-5