title: Molecular confirmation of the unique phenotype of epidermolysis bullosa simplex with mottled pigmentation.
abstract: BACKGROUND
  A distinctive subtype of epidermolysis bullosa simplex, with the additional feature of mottled pigmentation (EBS-MP), was initially characterized in a Swedish family in 1979, and seven further families have been reported. Features of EBS-MP that are observed in most affected patients include acral blistering early in childhood, mottled pigmentation distributed in a number of sites, focal punctate hyperkeratoses of the palms and soles, and dystrophic, thickened nails. The genetic basis of EBS-MP has been ascribed in five unrelated families to a heterozygous point mutation, P25L, in the non-helical V1 domain of K5.
  
  
  OBJECTIVE
  We report a clinical, ultrastructural and molecular study of two of the earliest families to be clinically characterized as EBS-MP.
  
  
  METHODS
  The P25L mutation was identified in all affected members of each of these families, bringing the total number of EBS-MP families with this mutation to seven.
  
  
  RESULTS
  This unusual recurrent mutation may uniquely cause EBS-MP.
  
  
  CONCLUSIONS
  While the exact molecular mechanisms by which this mutation causes epidermolysis, palmoplantar keratoderma and pigmentation remain elusive, we suggest possible molecular mechanisms through which the P25L substitution could cause this unusual phenotype.
authors.affiliation: Department of Dermatology, The Hospital for Children, Great Ormond Street, London WC1N 3JH, UK. irvo67@hotmail.com
authors.forename: A D
authors.initials: AD
authors.lastname: Irvine
authors.forename: E L
authors.initials: EL
authors.lastname: Rugg
authors.forename: E B
authors.initials: EB
authors.lastname: Lane
authors.forename: S
authors.initials: S
authors.lastname: Hoare
authors.forename: C
authors.initials: C
authors.lastname: Peret
authors.forename: A E
authors.initials: AE
authors.lastname: Hughes
authors.forename: A H
authors.initials: AH
authors.lastname: Heagerty
mesh_terms: D000293:Adolescent; D000328:Adult; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D017124:Conserved Sequence; D016110:Epidermolysis Bullosa Simplex / Q000150:complications / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D007633:Keratins / Q000235:genetics; D008297:Male; D010375:Pedigree; D010641:Phenotype; D010859:Pigmentation Disorders / Q000150:complications / Q000235:genetics* / Q000473:pathology; D017354:Point Mutation; D012867:Skin / Q000648:ultrastructure
chemical_list: D007633:Keratins