title: Mutations in the desmoglein 1 gene in five Pakistani families with striate palmoplantar keratoderma.
abstract: BACKGROUND
  Striate palmoplantar keratoderma (SPPK; OMIM #148700) is a rare autosomal dominant genodermatosis characterized by linear hyperkeratosis on the digits and hyperkeratosis on the palms and soles. SPPK is known to be caused by heterozygous mutations in either the desmoglein 1 (DSG1), desmoplakin (DSP), or keratin 1 (KRT1) genes.
  
  
  OBJECTIVE
  To define the molecular basis of SPPK in five Pakistani families showing a clear autosomal dominant inheritance pattern of SPPK.
  
  
  METHODS
  Based on previous reports of DSG1 mutations in SPPK, we performed direct sequencing of the DSG1 gene of all five families.
  
  
  RESULTS
  Mutation analysis resulted in the identification of one recurrent mutation (p.R26X) and four novel mutations (c.Ivs4-2A>G, c.515C>T, c.Ivs9-3C>G, and c.1399delA) in the DSG1 gene. Each mutation is predicted to cause haploinsufficiency of DSG1 protein.
  
  
  CONCLUSIONS
  The results of our study further underscore the significance of the desmoglein gene family in diseases of epidermal integrity.
authors.affiliation: Department of Dermatology, Columbia University, College of Physicians and Surgeons, 630 West 168th Street VC-1526, New York, NY 10032, United States.
authors.forename: Martha B
authors.initials: MB
authors.lastname: Dua-Awereh
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Shimomura
authors.forename: Liv
authors.initials: L
authors.lastname: Kraemer
authors.forename: Muhammad
authors.initials: M
authors.lastname: Wajid
authors.forename: Angela M
authors.initials: AM
authors.lastname: Christiano
mesh_terms: D001483:Base Sequence; D004247:DNA / Q000235:genetics; D051183:Desmoglein 1 / Q000235:genetics*; D051180:Desmoplakins / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D053556:Keratin-1 / Q000235:genetics; D007645:Keratoderma, Palmoplantar / Q000208:ethnology* / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics*; D010154:Pakistan; D010375:Pedigree; D012307:Risk Factors
chemical_list: D051183:Desmoglein 1; D051180:Desmoplakins; D053556:Keratin-1; D004247:DNA