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K. Nielsen, T. F. Orntoft, J. Hjortdal, N. Ehlers; Alteration in a Novel Domain of the Cytokeratin 12 Filament in Meesmann's Corneal Dystrophy. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1017.
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© ARVO (1962-2015); The Authors (2016-present)
To report a mutation that affects the novel domain 2A of the cytokeratin 12 filament in Meesmann's corneal dystrophy.
The diagnosis was based on slit-lamp biomicroscopy. DNA was isolated from blood samples from the family members. All exons of the cytokeratin 12 gene were sequenced in the oldest member of the family to identify the mutation. Exon 4 was subsequently sequenced for the remaining members.
Biomicroscopy showed numerous small reflective vesicles (microcysts) in the corneal epithelium. Molecular genetics revealed a novel mutation (929G→T) in exon 4 in all the family members with microcysts but not in members without microcysts. The missense-mutation gives rise to the putative amino acid substitution R302L in domain 2A of the intermediate filament. Hundred reference genomes were also sequenced to rule out the possibility of single nucleotide polymorphism.
Mutations causing Meesmann's corneal dystrophy are either affecting domain 1A or 2B of cytokeratin 12 or affecting cytokeratin 3. Our data suggest that alterations in the small central rod domain 2A may also be disease-causing. We propose that all exons should be sequenced when establishing a genetic diagnosis. Furthermore, this new information may help better to understand how cytokeratin dimers assemble.
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