A novel keratin 12 mutation in a German kindred wi th Meesmann's corneal dystrophy

Aim-To study a kindred with Meesmann's corneal dystrophy (MCD) to determine if a mutation within the cornea specific K3 or K12 genes is responsible fo r the disease phenotype. Methods-Slit lamp examination of the cornea in four members of the kindred was carried out to confirm the diagnosis of MCD. The region encoding the he lix initiation motif (HIM) of the K12 polypeptide was polymerase chain reac tion (PCR) amplified from genomic DNA derived from affected individuals in the kindred. PCR products generated were subjected to direct automated sequ encing. Restriction enzyme analysis employing Bait I was used to confirm th e presence of the mutation in affected individuals of the family. Results-Sequencing of the K12 gene in an affected individual from the famil y revealed a novel heterozygous missense mutation (413A-->C), predicting th e substitution of a proline for a glutamine at codon 130 (Q130P) in the HIM of the K12 protein. The mutation was excluded from 50 normal, unaffected i ndividuals by restriction enzyme analysis and was therefore unlikely to be a common polymorphism. Conclusion-A novel missense mutation in the K12 gene leads to MCD in a Germ an kindred. Missense mutations have now been identified within the region e ncoding the helix initiation motif of the K12 protein in eight of 11 MCD ki ndreds analysed at the molecular level.