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M. Oldak, J. P. Szaflik, A. Pollak, R. B. Maksym, M. Udziela, M. Uliska, R. Poski, J. Szaflik; Novel Mutation in the Keratin 3 Gene in a Family With Meesman Corneal Dystrophy. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1006. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the genetic background of Meesman corneal dystrophy (MCD) in a Polish family. MCD is characterized by fragility of the anterior corneal epithelium, which is morphologically manifested by intraepithelial microcysts. They appear in childhood and increase in number with age. Although the disease is generally benign and affected individuals are usually asymptomatic, some may suffer from recurrent erosions leading to lacrimation and photophobia. The disorder is dominantly inherited with incomplete penetrance. It is caused by mutations in keratin 3 (KRT3) or 12 (KRT12) genes encoding cornea-specific cytoskeletal proteins, which are important for the structural integrity of the epithelium. In the literature, 16 mutations in KRT12 and only 2 in KRT3 have been described so far.
We report on a 3-generation Polish family with MCD. Epithelial lesions characteristic for MCD were visualized with slit-lamp examination and confirmed by in vivo confocal microscopy. Using genomic DNA as a template all coding regions of KRT3 and KRT12 were amplified and sequenced. Presence of the mutation was verified with restriction endonuclease digestion.
Amplicon sequencing revealed the presence of a novel 1493A>T heterozygous missense mutation in exon 7 of KRT3, which predicts the substitution of a glutamic acid for a valine at codon 498 (E498V) in four family members. Applying the RFLP method the E498V mutation was excluded from over 70 normal controls from Polish population, indicating that it is not a common polymorphism.
Similarly to the previously published mutations in KRT3, the mutant codon is located at the C-terminus in the highly conserved alpha-helix termination motif. The region is required for keratin filament assembly, thus the amino acid substitution by changing the protein structure may disrupt the process of keratin filament formation leading to the development of MCD lesions.
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