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TGFBI (BIGH3) gene mutations in German families: two novel mutations associated with unique clinical and histopathological findings
  1. C Gruenauer-Kloevekorn1,
  2. I Clausen1,
  3. E Weidle2,
  4. M Wolter-Roessler3,
  5. F Tost4,
  6. H E Völcker5,
  7. D P Schulze6,
  8. W Heinritz7,
  9. T Reinhard8,
  10. U Froster7,
  11. G Duncker1,
  12. D Schorderet9,
  13. C Auw-Haedrich8
  1. 1
    Department of Ophthalmology, Martin Luther University, Halle, Germany
  2. 2
    Department of Ophthalmology, Katharinenhospital, Stuttgart, Germany
  3. 3
    Ophthalmic Surgery, Lauf, Germany
  4. 4
    Department of Ophthalmology, University of Greifswald, Greifswald, Germany
  5. 5
    Department of Ophthalmology, Ruprecht-Karl University, Heidelberg, Germany
  6. 6
    Klinikum Ernst von Bergmann, Potsdam, Germany
  7. 7
    Institute of Human Genetics, University of Leipzig, Leipzig, Germany
  8. 8
    Department of Ophthalmology, Albert-Ludwig University, Freiburg, Germany
  9. 9
    Institut de Recherche en Ophtalmologie, Sion, Switzerland
  1. Dr C Gruenauer-Kloevekorn, Department of Ophthalmology, Martin-Luther University, Ernst-Grube-Strasse 40, 06097 Halle, Germany; claudia.gruenauer-kloevekorn{at}


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.

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  • Competing interests: None.

  • Funding: This study was supported by the European Social Fund and the State of Sachsen-Anhalt, Germany.

  • Patient consent: Obtained.