title: Identification of two novel mutations in the cornea-specific TGFBI gene causing unique phenotypes in patients with corneal dystrophies.
abstract: The purpose of this study was to report on two novel missense mutations of the cornea-specific TGFBI gene in one single patient and in two generations of a family diagnosed with unique corneal dystrophy (CD) phenotypes. Ophthalmologic examination, in several cases ocular coherence tomography of the anterior segment (AS-OCT), was performed in 21 affected patients and in two unaffected members of one affected family. Coding regions of the TGFBI gene were direct sequenced in all 23 individuals. The two novel mutations were verified by RFLP analysis. A novel mutation c.1640T > G (p.Phe574Cys) in exon 12 of the TGFBI gene was detected in one single patient with recurrent granular intrastromal deposits comparable to a type of granular dystrophy. In AS-OCT, the deposit pattern reached up to the Descemet's layer. A further novel mutation c.393G > T(p.Glu131Asp) in exon 4 of the TGFBI gene was detected in all three affected members of one family with superficial cloud- and honeycomb-like opacifications, comparable to a Schnyder corneal dystrophy. Two unaffected members did not carry this alteration. The two identified novel mutations add other two phenotypes in patients suffering from TGFBI-linked CD to those reported so far. In one case, clinical finding indicates a Schnyder corneal dystrophy-like phenotype due to its superficial crystalline shape, and in the second one, granular deposits who reach Descemet's layer indicate a granular CD subtype. Molecular genetic analysis may help to distinguish those subtypes and to decide for specific treatment in time of a wide variation of corneal surgical techniques.
authors.affiliation: Department of Human Genetics, Martin-Luther-University Halle-Wittenberg, Magdeburger Str. 2, 06112, Halle, Germany. sabine.foja@uk-halle.de.
authors.forename: Sabine
authors.identifier: http://orcid.org/0000-0002-2703-5540
authors.initials: S
authors.lastname: Foja
authors.affiliation: Department of Human Genetics, Martin-Luther-University Halle-Wittenberg, Magdeburger Str. 2, 06112, Halle, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Hoffmann
authors.affiliation: Eye Center, Albert-Ludwigs-University Freiburg, Freiburg, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Auw-Haedrich
authors.affiliation: Eye Center, Albert-Ludwigs-University Freiburg, Freiburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Reinhard
authors.affiliation: Ophthalmic Surgery, Augenärzte am Markt, Halle, Germany.|Martin-Luther-University Halle-Wittenberg, Halle, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Rupprecht
authors.affiliation: Ophthalmic Surgery, Augenärzte am Markt, Halle, Germany.|Martin-Luther-University Halle-Wittenberg, Halle, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Gruenauer-Kloevekorn
mesh_terms: D000328:Adult; D003317:Corneal Dystrophies, Hereditary / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012189:Retrospective Studies; D053773:Transforming Growth Factor beta1 / Q000235:genetics*
chemical_list: D053773:Transforming Growth Factor beta1
keywords: Epithelial corneal dystrophy; Novel mutations; TGFBI gene