title: C-terminally truncated kindlin-1 leads to abnormal adhesion and migration of keratinocytes.
abstract: BACKGROUND
  The Kindler syndrome (KS) protein kindlin-1 is a member of a protein complex that links cortical actin to integrins on the surface of basal keratinocytes. Loss of kindlin-1 leads to abnormalities of cell adhesion and motility, and to skin blistering and progressive poikiloderma as clinical symptoms.
  
  
  OBJECTIVE
  Here we investigated a severely affected patient, disclosed the mutation that caused the disease and delineated its biological consequences.
  
  
  METHODS
  Mutation screening of the kindlin-1 gene, KIND1 (now called FERMT1), was performed with polymerase chain reaction (PCR) amplification of all exons and sequencing. Mutated kindlin-1 was characterized by reverse transcriptase (RT)-PCR and immunoblotting, and genotype-phenotype correlations were analysed using immunohistochemical staining of skin biopsies and keratinocytes from the patient's skin. Cell adhesion and motility were assessed with functional tests.
  
  
  RESULTS
  We disclosed a splice site mutation in the first position of intron 13 of the FERMT1 gene, which caused skipping of exon 13. The short transcript partially escaped nonsense-mediated mRNA decay and was translated into a truncated protein.
  
  
  CONCLUSIONS
  A C-terminally truncated kindlin-1 in keratinocytes could not function correctly even if it were expressed.
authors.affiliation: Department of Dermatology, University Medical Center Freiburg, Hauptstr. 7, 79104 Freiburg, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Has
authors.forename: R J
authors.initials: RJ
authors.lastname: Ludwig
authors.forename: C
authors.initials: C
authors.lastname: Herz
authors.forename: J S
authors.initials: JS
authors.lastname: Kern
authors.forename: S
authors.initials: S
authors.lastname: Ussar
authors.forename: F R
authors.initials: FR
authors.lastname: Ochsendorf
authors.forename: R
authors.initials: R
authors.lastname: Kaufmann
authors.forename: H
authors.initials: H
authors.lastname: Schumann
authors.forename: J
authors.initials: J
authors.lastname: Kohlhase
authors.forename: L
authors.initials: L
authors.lastname: Bruckner-Tuderman
mesh_terms: D000328:Adult; D002448:Cell Adhesion / Q000235:genetics*; D005091:Exons; D016368:Frameshift Mutation; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000166:cytology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012873:Skin Diseases, Genetic / Q000235:genetics / Q000473:pathology*
chemical_list: C475301:FERMT1 protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins