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

• Published in: American journal of ophthalmology 1998-10, Vol.126 (4), p.535-542
• Main Authors: Okada, Masaki, Yamamoto, Shuji, Tsujikawa, Motokazu, Watanabe, Hitoshi, Inoue, Yoshitsugu, Maeda, Naoyuki, Shimomura, Yoshikazu, Nishida, Kohji, Quantock, Andrew J, Kinoshita, Shigeru, Tano, Yasuo
• Format: Article
• Language: English
• Subjects: Adult; Biological and medical sciences; Cornea - pathology; Corneal Dystrophies, Hereditary - genetics; Corneal Dystrophies, Hereditary - pathology; Corneal Opacity - genetics; Corneal Opacity - pathology; DNA Mutational Analysis; DNA Primers - chemistry; Exons - genetics; Extracellular Matrix Proteins; Female; Humans; Male; Malformations of the eye; Medical sciences; Neoplasm Proteins - genetics; Ophthalmology; Pedigree; Point Mutation; Polymorphism, Single-Stranded Conformational; Sequence Analysis, DNA; Transforming Growth Factor beta - genetics; Visual Acuity
• ISSN: 0002-9394; 1879-1891
• DOI: 10.1016/S0002-9394(98)00135-4

PURPOSE: Two patients were diagnosed with Reis-Bücklers corneal dystrophy (RBCD), although the pattern and severity of corneal opacification differed. To see whether there was a genetic basis for these phenotypic variations, we analyzed βig-h3, the gene that codes for kerato-epithelin and that contains a mutation (Arg555Gln) that causes RBCD. METHODS: A 30-year-old man with honeycomb-shaped subepithelial opacities in his central cornea and a 25-year-old man with progressive subepithelial geographic opacities were both considered to have RBCD. We isolated genomic DNA from leukocytes of the two patients and their family members and screened for an Arg555Gln kerato-epithelin mutation. Then we analyzed all exons of the gene using the single-strand conformation polymorphism (SSCP) technique to search for any other kerato-epithelin mutations. RESULTS: The patient with honeycomb-shaped opacities had an Arg555Gln kerato-epithelin mutation that caused his RBCD, whereas the patient with geographic opacities did not; instead, he had a new kerato-epithelin mutation (Arg124Leu), which cosegregated with his family members. CONCLUSIONS: The variant of RBCD characterized by honeycomb-shaped opacities is caused by an Arg555Gln kerato-epithelin mutation. On the other hand, a new kerato-epithelin mutation, Arg124Leu, was found to cause the RBCD variant characterized by recurrent epithelial erosions and progressive geographic subepithelial opacification. Codon 124 is a hot spot for kerato-epithelin mutations, where the mutations responsible for three autosomal dominant corneal dystrophies—lattice type I (Arg124Cys), Avellino (Arg124His), and the variant of RBCD with geographic rather than honeycomb opacities (Arg124Leu)—are located.