SEVERE CORNEAL-DYSTROPHY PHENOTYPE CAUSED BY HOMOZYGOUS R124H KERATOEPITHELIN MUTATIONS

PURPOSE. To determine the mutational status of the beta ig-h3 gene in five patients from four Japanese families affected with an unusual, se vere form of corneal dystrophy. In these five cases, the corneas were remarkable for confluent round opacities in the superficial stromal la yer. The beta ig-h3 gene coding for keratoepithelin was recently ident ified as the gene responsible for Sq-linked autosomal dominant corneal dystrophies. METHODS. Genomic DNA was isolated from leukocytes of fiv e patients with the severe form of corneal dystrophy. To screen for po int mutations, exons of the beta ig-h3 gene were amplified by polymera se chain reaction and were analyzed with the single-strand conformatio nal polymorphism technique. Subsequently, the mutations were identifie d by a direct sequencing method and restriction enzyme digestion analy sis. RESULTS. All five patients with the severe form of corneal dystro phy had homozygous R124H keratoepithelin mutations. Histopathologic ex aminations of the corneas obtained from two patients with the severe f orm showed granular, rod-shaped deposits. CONCLUSIONS. The severe phen otype was a pathologic variant of granular corneal dystrophy (GCD). Al l five patients had homozygous R124H keratoepithelin mutations. The R1 24H keratoepithelin mutation is the same mutation recently reported to be responsible for Avellino corneal dystrophy. The homozygous R124H k eratoepithelin mutations are the cause of the severe variant of GCD ch aracterized by juvenile-onset and confluent superficial opacity.