title: Novel KIND1 gene mutation in Kindler syndrome with severe gastrointestinal tract involvement.
abstract: BACKGROUND
  Kindler syndrome (online Mendelian Inheritance in Man No. 173650) is an autosomal recessive genodermatosis characterized by acral trauma-induced blistering that improves with age and by progressive poikiloderma in later life. Other clinical features include photosensitivity, webbing of the fingers and toes, nail dystrophy, periodontal disease, and mucosal alterations. Aside from esophageal or anal stenosis, gastrointestinal tract involvement seems to be rare in Kindler syndrome. Recently, mutations in the KIND1 gene that encodes for the membrane-associated protein kindlin-1 have been identified. Kindlin-1 links the actin cytoskeleton to the extracellular matrix and is supposed to have cell-signaling functions owing to different functional domains. In particular, a domain with high homology to 4.1/ezrin/radixin/moesin (FERM) proteins is closely related to the sequences of talin that mediate integrin binding and therefore may play a role in integrin-dependent processes such as cell growth, differentiation, and apoptosis.
  
  
  METHODS
  Complete loss of this multifunctional protein in our patient with Kindler syndrome resulted in severe gastrointestinal tract involvement with hemorrhagic colitis. Mucosa of the descending and sigmoid colon and the rectum showed erosions and ulcers with pseudomembranous alterations of an overall highly vulnerable mucosa. Mutation analysis revealed a homozygous status for the novel mutation 20/21delTT in exon 2 of the KIND1 gene resulting in a preterminal stop codon creating a nonfunctional peptide 17 amino acids in length.
  
  
  CONCLUSIONS
  Because of our experience with this and another patient, we propose that gastrointestinal tract involvement should be looked at more frequently in Kindler syndrome.
authors.affiliation: Department of Dermatology, Paracelsus Private Medical University of Salzburg, Salzburg, Austria.
authors.forename: Elke
authors.initials: E
authors.lastname: Sadler
authors.forename: Alfred
authors.initials: A
authors.lastname: Klausegger
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Muss
authors.forename: Ursula
authors.initials: U
authors.lastname: Deinsberger
authors.forename: Gabriele
authors.initials: G
authors.lastname: Pohla-Gubo
authors.forename: Martin
authors.initials: M
authors.lastname: Laimer
authors.forename: Christoph
authors.initials: C
authors.lastname: Lanschuetzer
authors.forename: Johann W
authors.initials: JW
authors.lastname: Bauer
authors.forename: Helmut
authors.initials: H
authors.lastname: Hintner
mesh_terms: D000328:Adult; D001706:Biopsy; D003093:Colitis, Ulcerative / Q000150:complications / Q000235:genetics* / Q000473:pathology; D003113:Colonoscopy; D004247:DNA / Q000235:genetics*; D018450:Disease Progression; D016108:Epidermolysis Bullosa Dystrophica / Q000150:complications / Q000235:genetics* / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D046529:Microscopy, Electron, Transmission; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D011379:Prognosis; D012867:Skin / Q000648:ultrastructure; D013577:Syndrome
chemical_list: C475301:FERMT1 protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D004247:DNA