Meesmann Corneal Dystrophy (MECD): Report Of 2 Families and a Novel Mutation in the Cornea Specific Keratin KRT12 Gene

Abstract

Abstract: : Purpose: To identify the mutations involved in two families with MECD and establish a phenotype–genotype correlation Methods: Probands from 2 families were investigated because of photophobia. Blood for DNA extraction was obtained from all members after informed consent. The index patients were screened for mutation in the keratin 3 (KRT3) and keratin 12 (KRT12) genes. Exon 7 of KRT3 and exons 1 and 6 of KRT12 were PCR amplified and screened by DHPLC. Products with abnormal profile were directly sequenced on both strands Results: One case was referred to us for mutational analysis and was reported to have typical lesions of MECD. The second family was of Swiss origin and included 12 individuals over 4 generations. Affected members suffered from photophobia and the index patient had a best correct visual acuity of 0.8 both sides. Biomicroscopical examination revealed typical microcystic intraepithelial lesions over the whole cornea. In the first DNA, mutation analysis of KRT12 revealed a M129T present in a heterozygous state. In patients from the Swiss family, we identified a T to G transversion at position 3056 of the cDNA, in exon 6, replacing I426 by Serine. This mutation segregated in all available affected members and was not observed in 100 controls Conclusions: Our screening strategy is based on the sequential approach of both genes. First, we screen exon 7 of KRT3, then exons 1 and 6 of KRT12. The mutations of both families were observed in K12. M129T has already been reported (Corden et al. 2000). In the second family, we identified an I426S mutation in exon 6. Although I426 has already been mutated in MECD, it was into valine. This is a novel mutation and may represent the 12^th mutation reported so far in K12. All mutations are missense mutations, with subtle theoretical changes in the protein and they all fall either in KRT12 exon 1 or 6

Keywords: mutations • cornea: clinical science • gene screening