title: Mutations in the SLURP-1 gene underlie Mal de Meleda in three Pakistani families.
abstract: BACKGROUND
  Mal de Meleda (MDM) (MIM #248300) is an autosomal recessive palmoplantar keratoderma (PPK). It is characterized clinically by erythematous hyperkeratotic plaques over palms and soles that start early in life and progress later in life in a transgradiens form associated with pain, macerations, foul odor, pseudoainhum, brachydactyly, onychodystrophy and perioral erythema.
  
  
  OBJECTIVE
  To look for SLURP-1 gene mutations in patients with MDM.
  
  
  METHODS
  We collected peripheral blood samples from Pakistani family members affected with MDM and 100 population-matched unrelated healthy control individuals in EDTA-containing tubes. All exons of the SLURP-1 gene with adjacent sequences at exon-intron borders were amplified. The amplified PCR products were directly sequenced in an ABI Prism 310 Automated Sequencer. Screening assay, using the restriction enzyme HphI was performed.
  
  
  RESULTS
  We determined three mutations in the SLURP-1 gene: one novel mutation, c.Ivs1+1G>A, and two recurrent mutations, p.R96X and p.G86R. Screening assays for the novel mutation excluded the possibility of polymorphism. In vivo transcription assays showed that the mutation c.Ivs1+1G>A leads to aberrant splicing events.
  
  
  CONCLUSIONS
  Our results expand the spectrum of mutations in SLURP-1 gene.
authors.affiliation: Department of Dermatology, Columbia University, New York, NY, United States.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Wajid
authors.forename: Mazen
authors.initials: M
authors.lastname: Kurban
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Shimomura
authors.forename: Angela M
authors.initials: AM
authors.lastname: Christiano
mesh_terms: D000950:Antigens, Ly / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D005808:Genes, Recessive / Q000235:genetics; D006801:Humans; D007645:Keratoderma, Palmoplantar / Q000235:genetics* / Q000473:pathology; D008297:Male; D020125:Mutation, Missense / Q000235:genetics; D010375:Pedigree; D012867:Skin / Q000473:pathology; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics*
chemical_list: D000950:Antigens, Ly; C048963:SLURP1 protein, human; D014568:Urokinase-Type Plasminogen Activator