A novel mutation in the helix termination motif of keratin K12 in a US family with Meesmann corneal dystrophy

PURPOSE: Meesmann corneal dystrophy is an autosomal dominant disorder chara cterized by fragility of the anterior corneal epithelium. We have previousl y demonstrated that this disease can be caused by mutations in the genes en coding keratins K3 or K12, the major intermediate filament proteins express ed in corneal epithelial cells. Here, we have carried out mutation analysis in a United States kindred presenting with typical features of Meesmann co rneal dystrophy. METHODS: Exons 1 and 6 of the K12 gene (KRT12) were polymerase chain reacti on amplified from the proband's and control DNA and subjected to direct aut omated 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 an d excluded from 50 normal individuals by restriction enzyme analysis of pol ymerase chain reaction products. CONCLUSION: We report a novel mutation in a critical molecular overlap regi on of K12 in a United States family with Meesmann corneal dystrophy. The re sults confirm that mutations in the corneal keratins (K3 or K12) can underl ie Meesmann corneal dystrophy. (C) 1999 by Elsevier Science Inc. All rights reserved.