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Jacek P. Szaflik - One of the best experts on this subject based on the ideXlab platform.

  • Genetics of Meesmann Corneal Dystrophy: a novel mutation in the keratin 3 gene in an asymptomatic family suggests genotype-phenotype correlation.
    Molecular vision, 2008
    Co-Authors: Monika Ołdak, Radosław B. Maksym, Anna Kamińska, Agnieszka Pollak, Monika Udziela, Rafał Płoski, Jacek P. Szaflik
    Abstract:

    Purpose Juvenile epithelial Corneal Dystrophy of Meesmann (MCD, OMIM 122100) is a dominantly inherited disorder characterized by fragility of the anterior Corneal epithelium and intraepithelial microcyst formation. Although the disease is generally mild and affected individuals are often asymptomatic, some suffer from recurrent erosions leading to lacrimation, photophobia, and deterioration in visual acuity. MCD is caused by mutations in keratin 3 (KRT3) or keratin 12 (KRT12) genes, which encode cornea-specific cytoskeletal proteins. Seventeen mutations in KRT12 and two in KRT3 have been described so far. The purpose of this study was to investigate the genetic background of MCD in a Polish family. Methods We report on a three-generation family with MCD. Epithelial lesions characteristic for MCD were visualized with slit-lamp examination and confirmed by in vivo confocal microscopy. Using genomic DNA as a template, all coding regions of KRT3 and KRT12 were amplified and sequenced. Presence of the mutation was verified with restriction endonuclease digestion. Results In the proband, direct sequencing of the polymerase chain reaction (PCR) product from amplified coding regions of KRT3 and KRT12 revealed a novel 1493A>T heterozygous missense mutation in exon 7 of KRT3, which predicts the substitution of glutamic acid for valine at codon 498 (E498V). Using PCR-Restriction Fragment Length Polymorphism (RFLP) analysis, the mutation was demonstrated to segregate with the disease (four affected members, three non-affected) and to be absent in 100 controls from the Polish population, indicating that it is not a common polymorphism. Conclusions Location of the E498V mutation emphasizes the functional relevance of the highly conserved boundary motifs at the COOH-terminus of the alpha-helical rod domain in keratin 3 (K3).

Sheau-chiou Chao - One of the best experts on this subject based on the ideXlab platform.

W.h. Irwin Mclean - One of the best experts on this subject based on the ideXlab platform.

  • A novel mutation in the helix termination motif of keratin K12 in a US family with Meesmann Corneal Dystrophy.
    American journal of ophthalmology, 1999
    Co-Authors: Carrie M. Coleman, Sadeer B. Hannush, Seana P. Covello, Frances J.d. Smith, Jouni Uitto, W.h. Irwin Mclean
    Abstract:

    Abstract PURPOSE: Meesmann Corneal Dystrophy is an autosomal dominant disorder characterized by fragility of the anterior Corneal epithelium. We have previously demonstrated that this disease can be caused by mutations in the genes encoding keratins K3 or K12, the major intermediate filament proteins expressed in Corneal epithelial cells. Here, we have carried out mutation analysis in a United States kindred presenting with typical features of Meesmann Corneal Dystrophy. METHODS: Exons 1 and 6 of the K12 gene ( KRT12 ) were polymerase chain reaction amplified from the proband's and control DNA and subjected to direct automated sequencing. RESULTS: A heterozygous missense mutation 1300A→G was detected in exon 6 of KRT12 , predicting amino acid substitution I426V in the helix termination motif of the K12 polypeptide. The mutation was confirmed in the proband and excluded from 50 normal individuals by restriction enzyme analysis of polymerase chain reaction products. CONCLUSION: We report a novel mutation in a critical molecular overlap region of K12 in a United States family with Meesmann Corneal Dystrophy. The results confirm that mutations in the Corneal keratins (K3 or K12) can underlie Meesmann Corneal Dystrophy.

Hiroshi Tsuneoka - One of the best experts on this subject based on the ideXlab platform.

  • KRT12 Mutations and In Vivo Confocal Microscopy in Two Japanese Families With Meesmann Corneal Dystrophy
    American journal of ophthalmology, 2013
    Co-Authors: Mikihide Ogasawara, Yukihiro Matsumoto, Takaaki Hayashi, Kenji Ohno, Hisashi Yamada, Tetsuya Kawakita, Murat Dogru, Jun Shimazaki, Kazuo Tsubota, Hiroshi Tsuneoka
    Abstract:

    Purpose To identify genetic mutations and study the Corneal epithelium in Japanese patients with Meesmann Corneal Dystrophy. Design Laboratory investigation and prospective observational case series. Methods Slit-lamp biomicroscopy with fluorescein vital staining and in vivo confocal microscopy were performed. Mutation screening of the KRT3 and KRT12 genes was performed via polymerase chain reaction and direct sequencing for 5 patients in 2 families. Results Slit-lamp biomicroscopy revealed multiple Corneal intraepithelial microcysts in all patients. A clear zone was seen in the younger generation, whereas mild subepithelial opacity was seen in the older generation. In the in vivo confocal microscopy, numerous Corneal intraepithelial microcysts and hyperreflective materials, which were believed to be degenerative cells, were detected closer to the basal layer of the Corneal epithelium in older patients. The superficial layer contained more enlarged microcysts, and the hyperreflective materials showed atrophic changes, as compared to the basal layer. The demarcation line between the microcysts and normal epithelial cells was clearly visualized by in vivo confocal microscopy and corresponded to the demarcation line of the clear zone observed by the slit-lamp examination. Two heterozygous mutations (Q130P, L140Q) in the KRT12 gene, one of which (L140Q) was novel, were identified only in the affected patients of the families. Conclusions We identified a novel missense mutation of the KRT12 gene in Meesmann Corneal Dystrophy. The in vivo confocal microscopy examinations revealed previously unreported depth-dependent ultrastructural changes in the living cornea of Meesmann Corneal Dystrophy patients.

Ying-ting Chen - One of the best experts on this subject based on the ideXlab platform.