title: Under-recognition of acral peeling skin syndrome: 59 new cases with 15 novel mutations.
abstract: BACKGROUND
  Acral peeling skin syndrome (APSS) is a rare skin fragility disorder usually caused by mutations in the transglutaminase 5 gene (TGM5).
  
  
  METHODS
  We investigated the mutation spectrum of APSS in the U.K., Germany and Poland.
  
  
  RESULTS
  We identified 59 children with APSS from 52 families. The phenotype was readily recognizable, with some variation in severity both within and between families. Most cases had been misdiagnosed as the localized form of epidermolysis bullosa simplex (EBS-loc). Eighteen different TGM5 mutations were identified, 15 of which were novel. Eight mutations were unique to a single family, nine each occurred in two families, while the common p.Gly113Cys mutation linked to a second missense variant p.Thr109Met occurred in 47 of the 52 families and was homozygous in 28. Most patients were of nonconsanguineous white European origin.
  
  
  CONCLUSIONS
  We propose that APSS is under-reported and widely misdiagnosed as EBS-loc, with significant counselling implications as APSS is autosomal recessive while EBS-loc is dominant. We recommend screening for TGM5 mutations when EBS-loc is suspected but not confirmed by mutations in KRT5 or KRT14. Our report trebles the number of known TGM5 mutations. It provides further evidence that p.Gly113Cys is a founder mutation in the European population. This is consistent with the striking ethnic distribution of APSS in U.K., where the majority of patients are of nonconsanguineous white European origin, in contrast to the pattern of other recessive skin disorders.
authors.affiliation: Department of Dermatology, Birmingham Children's Hospital, Steelhouse Lane, Birmingham, B4 6NH, U.K.
authors.forename: W
authors.initials: W
authors.lastname: Szczecinska
authors.forename: D
authors.initials: D
authors.lastname: Nesteruk
authors.forename: K
authors.initials: K
authors.lastname: Wertheim-Tysarowska
authors.forename: D T
authors.initials: DT
authors.lastname: Greenblatt
authors.forename: D
authors.initials: D
authors.lastname: Baty
authors.forename: F
authors.initials: F
authors.lastname: Browne
authors.forename: L
authors.initials: L
authors.lastname: Liu
authors.forename: L
authors.initials: L
authors.lastname: Ozoemena
authors.forename: A
authors.initials: A
authors.lastname: Terron-Kwiatkowski
authors.forename: J A
authors.initials: JA
authors.lastname: McGrath
authors.forename: J E
authors.initials: JE
authors.lastname: Mellerio
authors.forename: J
authors.initials: J
authors.lastname: Morton
authors.forename: K
authors.initials: K
authors.lastname: Woźniak
authors.forename: C
authors.initials: C
authors.lastname: Kowalewski
authors.forename: C
authors.initials: C
authors.lastname: Has
authors.forename: C
authors.initials: C
authors.lastname: Moss
mesh_terms: D002648:Child; D003873:Dermatitis, Exfoliative / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D003937:Diagnosis, Differential; D016110:Epidermolysis Bullosa Simplex / Q000175:diagnosis; D018703:Founder Effect; D005820:Genetic Testing; D005858:Germany / Q000208:ethnology; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D053547:Keratin-14 / Q000235:genetics; D053555:Keratin-5 / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D010859:Pigmentation Disorders / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D011044:Poland / Q000208:ethnology; D012871:Skin Diseases / Q000151:congenital; D011503:Transglutaminases / Q000235:genetics*; D006113:United Kingdom / Q000208:ethnology
chemical_list: C507540:KRT14 protein, human; C503940:KRT5 protein, human; D053547:Keratin-14; D053555:Keratin-5; C418703:transglutaminase 5; D011503:Transglutaminases