Two distinct kerato-epithelin mutations in Reis-Bücklers corneal dystrophy

Area of Science:

• Ophthalmology
• Genetics
• Molecular Biology

Background:

• Reis-Bücklers corneal dystrophy (RBCD) is a rare inherited eye disease.
• Phenotypic variations in RBCD suggest potential underlying genetic heterogeneity.
• The beta ig-h3 gene, encoding kerato-epithelin, is implicated in RBCD.

Purpose of the Study:

• To investigate the genetic basis for differing clinical presentations of Reis-Bücklers corneal dystrophy.
• To identify mutations in the beta ig-h3 gene in two patients with distinct RBCD phenotypes.

Main Methods:

• Genomic DNA was isolated from two patients with RBCD and their families.
• Screening for the known Arg555Gln kerato-epithelin mutation was performed.
• Single-strand conformation polymorphism (SSCP) analysis was used to screen all exons of the beta ig-h3 gene for novel mutations.

Main Results:

• The patient with honeycomb-shaped opacities carried the Arg555Gln kerato-epithelin mutation.
• The patient with geographic opacities did not have the Arg555Gln mutation.
• A novel kerato-epithelin mutation, Arg124Leu, was identified in the patient with geographic opacities and segregated with his family.

Conclusions:

• The Arg555Gln kerato-epithelin mutation is associated with the honeycomb variant of RBCD.
• The novel Arg124Leu kerato-epithelin mutation causes a distinct RBCD variant with geographic opacities and recurrent erosions.
• Codon 124 of the beta ig-h3 gene is a mutational hotspot for various autosomal dominant corneal dystrophies.