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Katherine Gee, Benjamin Ray Lin, Jessica Gee, Chulaluck Tangmonkongvoragul, Anthony J Aldave; Identification of a presumed pathogenic KRT3 gene mutation associated with Meesmann corneal dystrophy. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2530.
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© ARVO (1962-2015); The Authors (2016-present)
To report a potentially pathogenic mutation in the keratin 3 gene (KRT3) in an individual with clinically diagnosed Meesmann corneal dystrophy (MCD).
Slit lamp examination was performed prior to obtaining informed consent. A saliva specimen was collected as a source of genomic DNA. PCR amplification and Sanger sequencing of the 9 exons of KRT3 and the 8 exons of the keratin 12 gene (KRT12) was performed to identify coding region sequence variants. Polyphen-2 was used to predict the functional impact of identified variants.
A 60 year old man with a history of a corneal epitheliopathy since age 2 demonstrated bilateral, diffusely distributed, clear epithelial microcysts consistent with MCD. Screening of KRT3 revealed four heterozygous missense variants and one synonymous substitution, while screening of KRT12 demonstrated one heterozygous missense variant. Each identified variant has been reported to be present in >5% of the population with the exception of c.250C>T (p.(Arg84Trp)) in exon 1 of KRT3, which has a minor allele frequency (MAF) of 0.0076. This variant was not identified in more than 150 control chromosomes and is predicted to be damaging by in silico analysis using Polyphen-2.
We report a potentially pathogenic missense mutation (p.(Arg84Trp)) in KRT3 associated with MCD. This represents only the fourth mutation in KRT3 to be associated with MCD and the first potentially pathogenic mutation in the head domain of KRT3 exon 1.
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