title: Genetics of Meesmann corneal dystrophy: a novel mutation in the keratin 3 gene in an asymptomatic family suggests genotype-phenotype correlation.
abstract: OBJECTIVE
  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).
authors.affiliation: Department of Ophthalmology, Medical University of Warsaw, Warsaw, Poland. jacek@amwaw.edu.pl
authors.forename: Jacek P
authors.initials: JP
authors.lastname: Szaflik
authors.forename: Monika
authors.initials: M
authors.lastname: Ołdak
authors.forename: Radosław B
authors.initials: RB
authors.lastname: Maksym
authors.forename: Anna
authors.initials: A
authors.lastname: Kamińska
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Pollak
authors.forename: Monika
authors.initials: M
authors.lastname: Udziela
authors.forename: Rafał
authors.initials: R
authors.lastname: Płoski
authors.forename: Jerzy
authors.initials: J
authors.lastname: Szaflik
mesh_terms: D000328:Adult; D000368:Aged; D001483:Base Sequence; D053559:Corneal Dystrophy, Juvenile Epithelial of Meesmann / Q000235:genetics*; D004252:DNA Mutational Analysis; D019573:Epithelium, Corneal / Q000378:metabolism / Q000473:pathology; D005091:Exons / Q000235:genetics; D005190:Family; D005260:Female; D006579:Heterozygote; D006801:Humans; D053551:Keratin-12 / Q000235:genetics; D053558:Keratin-3 / Q000235:genetics*; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D011044:Poland; D044465:White People / Q000235:genetics
chemical_list: D053551:Keratin-12; D053558:Keratin-3