A novel arginine substitution mutation in 1A domain and a novel 27 bp insertion mutation in 2B domain of keratin 12 gene associated with Meesmann’s corneal dystrophy

摘要

>Aim: To determine the disease causing gene defects in two patients with Meesmann’s corneal dystrophy. >Methods: Mutational analysis of domains 1A and 2B of the keratin 3 (K3) and keratin 12 (K12) genes from two patients with Meesmann’s corneal dystrophy was performed by polymerase chain reaction amplification and direct sequencing. >Results: Novel mutations of the K12 gene were identified in both patients. In one patient a heterozygous point mutation (429A→C = Arg135Ser) was found in the 1A domain of the K12 gene. This mutation was confirmed by restriction digestion. In the second patient a heterozygous 27 bp duplication was found inserted in the 2B domain at nucleotide position 1222 (1222ins27) of the K12 gene. This mutation was confirmed by gel electrophoresis. The mutations were not present in unaffected controls. >Conclusion: Novel K12 mutations were linked to Meesmann’s corneal dystrophy in two different patients. A missense mutation replacing a highly conserved arginine residue in the beginning of the helix initiation motif was found in one patient, and an insertion mutation, consisting of a duplication of 27 nucleotides, was found before the helix termination motif in the other.