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In vivo histology and p.L132V mutation in KRT12 gene in Japanese patients with Meesmann corneal dystrophy

  • Tsubasa Nishino
  • Akira Kobayashi
  • Natsuko Mori
  • Toshinori Masaki
  • Hideaki Yokogawa
  • Keiko Fujiki
  • Ai Yanagawa
  • Akira Murakami
  • Kazuhisa Sugiyama
Clinical Investigation
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Abstract

Purpose

To report genetic mutational analysis and in vivo histology of Meesmann corneal dystrophy.

Study design

Prospective, case control study.

Methods

Six patients from three independent families with clinically diagnosed Meesmann corneal dystrophy were enrolled in this study. Slit-lamp biomicroscopy with fluorescein vital staining, anterior segment optical coherence tomography (AS-OCT), and in vivo laser confocal microscopy (IVCM) were performed on selected patients. Mutational screening for the keratin genes KRT3 and KRT12 was performed in all six patients and selected unaffected family members.

Results

Slit-lamp biomicroscopy revealed numerous intraepithelial microcysts in all affected individuals. AS-OCT revealed hyperreflectivity and high corneal epithelial layer thickness (mean, 64.8μm) in all individuals tested (3/3). By using IVCM, multiple epithelial microcysts and hyperreflective materials (6/6), subepithelial nerve abnormalities (6/6), tiny punctate hyperreflective material (6/6), and needle-like hyperreflective materials (4/6) were observed in the corneal stromal layer. A heterozygous genetic mutation in the KRT12 gene (c.394 C>G, p.L132V) was identified in all six patients. No pathological mutation was observed in the KRT3 gene.

Conclusion

We identified a heterozygous genetic mutation (c.394 C>G, p.L132V) in the KRT12 gene in six Japanese patients with inherited Meesmann corneal dystrophy. This is the first study to confirm this genetic mutation in Japanese Meesmann corneal dystrophy patients. This mutation has been independently reported in an American Meesmann corneal dystrophy patient, confirming its pathogenicity. AS-OCT and IVCM proved to be useful tools for observing corneal epithelial layer pathology in this dystrophy. Furthermore, IVCM reveals corneal stromal layer pathological changes not previously reported in this dystrophy.

Keywords

Meesmann corneal dystrophy Anterior segment optical coherence tomography In vivo confocal microscopy Genetic mutation analysis Corneal epithelium 

Notes

Funding

Financial support: Grant-in-Aid for Scientific Research (C) KAKENHI, Japan (No. 16K11261).

Conflicts of interest

T. Nishino, None; A. Kobayashi, None; N. Mori, None; T. Masaki, None; H. Yokogawa, None; K. Fujiki, None; A. Yanagawa, None; A. Murakami, None; K. Sugiyama, None.

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Copyright information

© Japanese Ophthalmological Society 2018

Authors and Affiliations

  • Tsubasa Nishino
    • 1
  • Akira Kobayashi
    • 1
  • Natsuko Mori
    • 1
  • Toshinori Masaki
    • 1
  • Hideaki Yokogawa
    • 1
  • Keiko Fujiki
    • 2
  • Ai Yanagawa
    • 2
  • Akira Murakami
    • 2
  • Kazuhisa Sugiyama
    • 1
  1. 1.Department of OphthalmologyKanazawa University Graduate School of Medical ScienceKanazawaJapan
  2. 2.Department of OphthalmologyJuntendo University Graduate School of Medical ScienceTokyoJapan

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