KRT12 gene

Overview

Gene (OMIM No.)	KRT12 (#601687)
Function of gene/protein	Protein: Cytokeratin 12 Expressed in the corneal epithelium Forms intermediate filaments with cytokeratin 3, which are integral to the mechanical strength and support of the epithelial cells
Clinical phenotype (OMIM phenotype no.)	Meesmann corneal dystrophy 1 (#122100)
Inheritance	Autosomal dominant
Ocular features	Intraepithelial microcysts (best visualised on retro-illumination) The cysts may rupture leading to recurrent painful epithelial erosions Cysts do not stain with fluorescein except when it has broken through to the surface
Systemic features	No systemic features reported
Key investigations	Usually diagnosed on slit lamp examination alone Anterior segment OCT: Hyper-reflective vacuoles measuring about 50𝜇m diameter
Molecular diagnosis	Next generation sequencing Targeted gene panels (ASD) Whole exome sequencing Whole genome sequencing
Management	Management of Meesmann epithelial corneal dystrophy
Therapies under research	Gene silencing with allele-specific short-interfering RNA (siRNA) molecules Gene editing with CRISPR/Cas9 technology
Further information	Medline Plus

Allen EH, Courtney DG, Atkinson SD, et al. Keratin 12 missense mutation induces the unfolded protein response and apoptosis in Meesmann epithelial corneal dystrophy. Hum Mol Genet. 2016;25(6):1176-1191
Herrmann H, Aebi U. Intermediate Filaments: Structure and Assembly. Cold Spring Harb Perspect Biol. 2016 Nov 1;8(11):a018242
Irvine AD, Corden LD, Swensson O, et al. Mutations in cornea-specific keratins K3 or K12 cause Meesmann’s corneal dystrophy. Nat Genet. 1997;16: 184–187
Irvine AD, Coleman CM, Moore JE, et al. A novel mutation in KRT12 associated with Meesmann’s epithelial corneal dystrophy. Br J Ophthalmol. 2002;86: 729–732
Chen JL, Lin BR, Gee KM, et al. Identification of presumed pathogenic KRT3 and KRT12 gene mutations associated with Meesmann corneal dystrophy. Mol Vis. 2015;21:1378-1386
Liao H, Irvine AD, Macewen CJ, et al. Development of allele-specific therapeutic siRNA in Meesmann epithelial corneal dystrophy. PLoS One. 2011;6(12):e28582
Courtney DG, Moore JE, Atkinson SD, Maurizi E, Allen EH, Pedrioli DM, McLean WH, Nesbit MA, Moore CB. CRISPR/Cas9 DNA cleavage at SNP-derived PAM enables both in vitro and in vivo KRT12 mutation-specific targeting. Gene Ther. 2016 Jan;23(1):108-12

Updated on November 30, 2020