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

Abstract

Purpose: To report a novel missense mutation of the cornea specific keratin 12 (KRT12) gene in two generations of a German family diagnosed with Meesmann;s 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 Meesmann;s corneal dystrophy in a German family.

Figure 1

Scheme of the KRT3 structure. The localizations of the known point mutations within the helix-termination motif are indicated.

Figure 2

Scheme of the KRT12 structure. The localizations of the known point mutations within the helix-initiation and the helix-termination motif are indicated.

Figure 3

Slit lamp photography of patient I/2. The corneal epithelium showed bilateral myriads of fine cysts predominantly in the center of the cornea (A=right eye, B=left eye).

Figure 4

Chromatogram of the heterozygous 409G>A mutation at codon 129 in the keratin 12 gene of patient I/2.

Figure 5

Chromatogram of the single point polymorphism 67C>T in the keratin 12 gene of patient I/2.

Figure 6

Pedigree of the examined German family. Below results of restriction enzyme analysis after HpyCH4III digestion on a 2% agarose gel stained with ethidium bromide. In the presence of the 409G>A mutation the full PCR fragment of 369 bp is cut into bands of 293 and 76 bp (the latter not shown) as seen in the proband (I/2) and her two affected sons (II/1, II/2). Undigested DNA was seen in the unaffected husband (I/1).