KRT12 gene

Overview

Gene (OMIM No.)
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.)
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 diagnosisNext generation sequencing
  • Targeted gene panels (ASD)
  • Whole exome sequencing
  • Whole genome sequencing
Management
Therapies under research
  • Gene silencing with allele-specific short-interfering RNA (siRNA) molecules
  • Gene editing with CRISPR/Cas9 technology
Further information

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References

  1.  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
  2.  Herrmann H, Aebi U. Intermediate Filaments: Structure and Assembly. Cold Spring Harb Perspect Biol. 2016 Nov 1;8(11):a018242
  3.  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
  4.  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
  5.  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
  6.  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
  7.  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

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Updated on November 30, 2020
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