A novel mutation of the Keratin 12 gene responsible for asevere phenotype of Meesmann's corneal dystrophy

[摘要] Purpose: To determine if a mutation within the coding region of thekeratin 12 gene (KRT12) is responsible for a severe form ofMeesmann's corneal dystrophy.Methods: A family with clinically identified Meesmann's cornealdystrophy was recruited and studied. Electron microscopy was performedon scrapings of corneal epithelial cells from the proband. Mutations inthe KRT12 gene were sought using direct genomic sequencing ofleukocyte DNA from two affected and two unaffected family members.Subsequently, the observed mutation was screened in all available familymembers using polymerase chain reaction and direct sequencing.Results: A heterozygous missense mutation (Arg430Pro) was found inexon 6 of KRT12 in all 14 affected individuals studied. Unaffectedfamily members and 100 normal controls were negative for this mutation.Conclusions: We have identified a novel mutation in the KRT12gene that is associated with a symptomatic phenotype of Meesmann'scorneal dystrophy. This mutation results in a substitution of prolinefor arginine in the helix termination motif that may disrupt the normalhelix, leading to a dramatic structural change of the keratin 12protein.

[学科分类] 生物化学/生物物理