Identification of a novel mutation in the cornea specific keratin 12 gene causing Meesmann's corneal dystrophy in a German family.

Purpose: To report a novel missense mutation of the cornea specific keratin 12 (KRT12) gene in two generations of a German family diagnosed with Meesmanns corneal dystrophy. Methods: Ophthalmologic examination of the proband and sequencing of keratin 3 (KRT3) and KRT12 of the proband and three other family members were performed. Restriction enzyme analysis was used to confirm the detected mutation in affected individuals of the family. Results: Slit-lamp biomicroscopy of the proband revealed multiple intraepithelial microcysts comparable to a Meesmann dystrophy phenotype. A novel heterozygous A→G transversion at the first nucleotide position of codon 129 (ATG>GTG, M129V) in exon 1 of KRT12 was detected in the proband, her two affected sons but not in her unaffected husband or 50 control individuals. Conclusions: We have identified a novel missense mutation within the highly conserved helix-initiation motif of KRT12 causing Meesmanns corneal dystrophy in a German family. The cornea represents the anterior surface of the eye and must maintain its structural integrity as well as its transparency to retain good vision. The outermost layer of the cornea is presented by the corneal epithelium. In 1939 the German ophthalmologists Meesmann and Wilke described a dominantly inherited dystrophy affecting the corneal epithelium in three families living in northern Germany (1). The 34 affected family members showed ocular irritation, tearing, and glare. Slit lamp biomicroscopy revealed myriads of microcystic epithelial opacities extending to the corneal limbus. Twenty-six years after the initial report by Meesmann and Wilke, Behnke and Thiel (2) published an extensive study of the same three northern German families. Kuwabara and Ciccarelli (3) were the first who examined the ultrastructure of the cornea from patients with Meesmanns corneal dystrophy (MECD; OMIM 122100) in 1964. They were followed by Fine et al. (4) in 1977 and Tremblay and Dube (5) in 1982. The authors described the corneal epithelial basement membrane as thickened with an intracellular "peculiar substance" that reacted with periodic acid and Schiffs reagent. This substance appeared to be derived from the tonofilaments.