In vivo histology and p.L132V mutation in KRT12 gene in Japanese patients with Meesmann corneal dystrophy
- 107 Downloads
To report genetic mutational analysis and in vivo histology of Meesmann corneal dystrophy.
Prospective, case control study.
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.
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.
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.
KeywordsMeesmann corneal dystrophy Anterior segment optical coherence tomography In vivo confocal microscopy Genetic mutation analysis Corneal epithelium
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.
- 1.Meesmann A, Wilke F. Klinische und anatomische Untersuchungen ueber eine bisher unbekannte, dominant vererbte Epitheldystrophie der Hornhaut. Klin Mbl Augenheilk. 1939;103:361–91 (in German).Google Scholar
- 12.Aldave AJ. The clinical utility of genetic analysis in the diagnosis and management of inherited corneal disorders. Contemp Ophthalmol. 2005;4:1–10.Google Scholar
- 13.Wang LJ, Tian X, Zhang QS, Liu L. Analysis of mutation in KRT12 gene in a Chinese family with Meesmann’s corneal dystrophy. Zhonghua Yan Ke Za Zhi. 2007;43:885–9 (in Chinese).Google Scholar
- 14.Sullivan LS, Baylin EB, Font R, Daiger SP, Pepose JS, Clinch TE, et al. A novel mutation of the Keratin 12 gene responsible for a severe phenotype of Meesmann’s corneal dystrophy. Mol Vis. 2007;13:975–80.Google Scholar
- 15.Szaflik JP, Ołdak M, Maksym RB, Kamińska A, Pollak A, Udziela M, et al. Genetics of Meesmann corneal dystrophy: a novel mutation in the keratin 3 gene in an asymptomatic family suggests genotype-phenotype correlation. Mol Vis. 2008;14:1713–8.Google Scholar
- 19.Clausen I, Duncker GI, Grünauer-Kloevekorn C. Identification of a novel mutation in the cornea specific keratin 12 gene causing Meesmann’s corneal dystrophy in a German family. Mol Vis. 2010;16:954–60.Google Scholar
- 27.Javadi MA, Rezaei-Kanavi M, Javadi A, Naghshgar N. Meesmann corneal dystrophy; a clinico-pathologic, ultrastructural and confocal scan report. J Ophthalmic Vis Res. 2010;5:122–6.Google Scholar
- 28.McLean WH, Irvine AD. Disorders of keratinisation: from rare to common genetic diseases of skin and other epithelial tissues. Ulster Med J. 2007;76:72–82.Google Scholar