[Analysis of mutation in KRT12 gene in a Chinese family with Meesmann's corneal dystrophy].

OBJECTIVE

To investigate the mutation of KRT12 gene in a large Chinese family with Meesmann's corneal dystrophy by molecular genetic study and linkage analysis.

METHODS

Mode of inheritance was determined in a family with Meesmann's corneal dystrophy provided by Xingtai Eye Hospital. The blood samples were obtained from members of this family, including both affected and unaffected members. The genome-DNA was extracted from the samples. Linkage analysis was conducted in the selected markers (D17S800, D17S930, D12S390, D12S96) in the locus around KRT12 and KRT3 genes. The exons of linked genes were sequenced directly. All of the members in this family were examined with slit lamp biomicroscope and photographed. Blood samples were collected from 100 normal subjects and analyzed as the controls.

RESULTS

The mode of inheritance of corneal dystrophy in this family was identified as autosomal dominant inheritance. The clinical diagnosis was Meesmann's corneal dystrophy. Linkage analysis revealed a lod score of 2.41 with theta = 0.00 at markers D17S800 and D17S930. Linkage was revealed between corneal dystrophy and KRT12 gene. Sequences of KRT12 gene in affected members showed the mutant in exon 1, T419A and L132H. All affected members in this family were heterozygotes of this mutation. No mutation of this type was identified in all unaffected member of this family and in the 100 normal controls.

CONCLUSION

Mutation of KRT12 gene in exon 1, T419A and L132H is the molecular genetic change leading to the occurrence of Meesmann's corneal dystrophy in this Chinese family.