title: TGFBI (BIGH3) gene mutations in German families: two novel mutations associated with unique clinical and histopathological findings.
abstract: BACKGROUND
  To report the clinical, histopathological and immunohistochemical findings of two novel mutations within the TGFBI gene.
  
  
  METHODS
  The genotype of 41 affected members of 16 families and nine sporadic cases was investigated by direct sequencing of the TGFBI gene. Clinical, histological and immunohistochemical characteristics of corneal opacification were reported and compared with the coding region changes in the TGFBI gene.
  
  
  RESULTS
  A novel mutation Leu509Pro was detected in one family with a geographic pattern-like clinical phenotype. Histopathologically we found amyloid together with non-amyloid deposits and immunohistochemical staining of Keratoepithelin (KE) KE2 and KE15 antibodies. In two families and one sporadic case the novel mutation Gly623Arg with a late-onset, map-like corneal dystrophy was identified. Here amyloid and immunohistochemical staining of only KE2 antibodies occurred. Further, five already known mutations are reported: Arg124Cys Arg555Trp Arg124His His626Arg, Ala546Asp in 13 families and five sporadic cases of German origin. The underlying gene defect within the TBFBI gene was not identified in any of the four probands with Thiel-Behnke corneal dystrophy.
  
  
  CONCLUSIONS
  The two novel mutations within the TGFBI gene add another two phenotypes with atypical immunohistochemical and histopathological features to those so far reported.
authors.affiliation: Department of Ophthalmology, Martin-Luther University, Ernst-Grube-Strasse 40, 06097 Halle, Germany. claudia.gruenauer-kloevekorn@medizin.uni-halle.de
authors.forename: C
authors.initials: C
authors.lastname: Gruenauer-Kloevekorn
authors.forename: I
authors.initials: I
authors.lastname: Clausen
authors.forename: E
authors.initials: E
authors.lastname: Weidle
authors.forename: M
authors.initials: M
authors.lastname: Wolter-Roessler
authors.forename: F
authors.initials: F
authors.lastname: Tost
authors.forename: H E
authors.initials: HE
authors.lastname: Völcker
authors.forename: D P
authors.initials: DP
authors.lastname: Schulze
authors.forename: W
authors.initials: W
authors.lastname: Heinritz
authors.forename: T
authors.initials: T
authors.lastname: Reinhard
authors.forename: U
authors.initials: U
authors.lastname: Froster
authors.forename: G
authors.initials: G
authors.lastname: Duncker
authors.forename: D
authors.initials: D
authors.lastname: Schorderet
authors.forename: C
authors.initials: C
authors.lastname: Auw-Haedrich
mesh_terms: D000328:Adult; D000367:Age Factors; D003317:Corneal Dystrophies, Hereditary / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D016212:Transforming Growth Factor beta / Q000235:genetics*; D014792:Visual Acuity / Q000235:genetics*; D055815:Young Adult; D000099222:betaIG-H3 Protein
chemical_list: D016326:Extracellular Matrix Proteins; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein