Late-onset lattice corneal dystrophy without typical lattice lines caused by a novel mutation in the TGFBI gene.
OBJECTIVE
The aim of this study was to report the clinical, histopathological, and molecular findings in a patient with late-onset lattice corneal dystrophy (LCD) without typical lattice lines and a novel mutation in the TGFBI gene.


METHODS
Corneal lesions were visualized by slit-lamp examination and by in vivo confocal microscopy. Histopathological examination was performed on the patient's corneal specimen obtained during a deep anterior lamellar keratoplasty. By using genomic DNA as a template, all coding regions of the TGFBI gene were amplified and directly sequenced. The presence of the mutation was verified using restriction endonuclease digestion. Eight different computational methods and multiple sequence alignments were used to predict the pathogenicity of the novel genetic variant.


RESULTS
The corneal phenotype was characterized by the presence within the stroma of round, oval, and short comma-shaped structures with indistinct margins. Lattice lines were not visible. Histopathological study revealed positive Congo red areas of amyloid deposits typical for LCD. A novel heterozygous missense mutation p.Leu565Pro was identified in exon 13 of the TGFBI gene. The amino acid substitution was unambiguously predicted to have a high pathogenic potential.


CONCLUSIONS
The mutant codon 565 is located at the C-terminus in the region corresponding to a highly conserved amino acid in the fourth fascilin domain of the TGFBI protein. The novel variant expands the spectrum of TGFBI mutations causing LCD and located in this region. An increased number of known mutations will facilitate future studies of genotype-phenotype correlations and molecular pathogenesis of corneal dystrophies.
Departments of *Histology and Embryology; and †Ophthalmology, Medical University of Warsaw, Warsaw, Poland; ‡Department of Ophthalmology, Medical University of Lublin, Lublin, Poland; §Department of Ophthalmology, University of Erlangen-Nürnberg, Erlangen, Germany; and ¶Department of Medical Genetics, Medical University of Warsaw, Warsaw, Poland.
Monika
M
Ołdak
Jacek P
JP
Szaflik
Aneta
A
Ścieżyńska
Monika
M
Udziela
Radosław B
RB
Maksym
Beata
B
Rymgayłło-Jankowska
Carmen
C
Hofmann-Rummelt
Johannes
J
Menzel-Severing
Rafał
R
Płoski
Tomasz
T
Żarnowski
Friedrich E
FE
Kruse
Jerzy
J
Szaflik
D000368:Aged; D003317:Corneal Dystrophies, Hereditary / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D016039:Corneal Transplantation; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D016212:Transforming Growth Factor beta / Q000235:genetics*; D000099222:betaIG-H3 Protein
D016326:Extracellular Matrix Proteins; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein