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C. Auw-Haedrich, H. Agostini, I. Clausen, T. Reinhard, P. Eberwein, D. Schorderet, C. Gruenauer-Kloevekorn; A Unique Variant of Corneal Dystrophy of Bowman's Layer Associated With TGFBI Gly623Asp Mutation: Amyloidogenic Phenotype in a German Family. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1010. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To present the light- and electronmicroscopical findings of a unique corneal dystrophy, which were not described before, in a German family carrying the Gly623Asp Mutation of the TGFBI gene.
5 corneal buttons of 3 affected siblings of an affected mother by history were excised at the time of penetrating keratoplasty. Light and electron microscopic examination were performed including immunohistochemistry with antibodies against Keratoepithelin (KE) 2 and 15. Slit lamp examination and isolation of genomic DNA from peripheral blood leucocytes obtained from 4 affected and 5 non-affected family members were carried out, individual exons of the TGFBI gene were amplified and sequenced.
The specimens showed destructive changes of the Bowman's layer and the adjacent stroma. Patchy Congo red-positive amyloid deposits were found within the epithelium in one cornea, in the Bowman's layer and the anterior stroma in all specimens, also showing KE2- but not KE15-immunostaining. Electron microscopy revealed electron dense ribbon-like and patchy deposits especially located in the anterior stroma and in the Bowman's layer and in small amounts in the basal area of some epithelial cells. The destructed areas were strongly Alcian blue-positiv, the Masson-Trichrom-stain proved mainly negative for the deposits. All affected but none of the unaffected family members had a heterozygous missense mutation in exon 14 of the TGFBI gene (G->A transition at nucleotide 1915) leading to of glycin to aspartic acid amino acid change (Gly623Asp) at position 623 of the keratoepithelin protein.
In contrast to the family carrying the Gly623Asp Mutation of the TGFBI gene described by Afshari et al. (the family reported by Aldave et al. with different clinical phenotype was not examined histologically), our specimens contained KE-2 positive amyloid which is in accordance to the TGFBI-mutation Gly623Asp. The reason for this -now "meeting the expectation histological phenotype"-is unclear. The histological findings emphasize that this is a unique corneal dystrophy which only share some clinical characteristics with Reis-Buecklers dystrophy and should be treated as a distinct entity.
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