title: A new L527R mutation of the betaIGH3 gene in patients with lattice corneal dystrophy with deep stromal opacities.
abstract: Mutations in the betaIGH3 gene on chromosome 5q31 cause five distinct autosomal dominant corneal dystrophies: granular Groenouw type I, Reis-Bücklers', lattice type I and IIIA. and Avellino corneal dystrophies. We present here a new mutation of the betaIGH3 gene in patients with late-onset lattice corneal dystrophy manifest as a deep stromal opacity. To test the previously reported R124C, R124H, P501T, R555W, and R555Q mutations of the betaIGH3 gene, 30 patients and 11 normal relatives from 16 independently ascertained families with lattice corneal dystrophy, 49 patients and 12 normal relatives from 40 independently ascertained families with other corneal dystrophies, and 40 unrelated normal volunteers, were analyzed. A L527R (CTG/CGG) mutation of the betaIGH3 gene was found in 6 unrelated patients with lattice corneal dystrophy. A retrospective review of the patients' records showed that the opacities were deep in the stromal layer and of late onset. The mutation was a heterozygous single base-pair transversion from T to G of the second nucleotide position of codon 527. This caused the substitution of arginine for leucine. These six patients did not have mutations in codons 124, 501, or 555. The L527R mutation was not detected in the other corneal dystrophies or 40 normal volunteers. Although phenotypic variations in the size and shape of the deposits were found, all patients with the L527R mutation showed deposits deep in the stromal layer. We conclude that there are now at least six different mutations that have been detected in the betaIGH3 gene on chromosome 5q31 and that lead to corneal dystrophy.
authors.affiliation: Department of Ophthalmology, Juntendo University School of Medicine, Tokyo, Japan. fujiki@med.juntendo.ac.jp
authors.forename: K
authors.initials: K
authors.lastname: Fujiki
authors.forename: Y
authors.initials: Y
authors.lastname: Hotta
authors.forename: K
authors.initials: K
authors.lastname: Nakayasu
authors.forename: T
authors.initials: T
authors.lastname: Yokoyama
authors.forename: T
authors.initials: T
authors.lastname: Takano
authors.forename: T
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: A
authors.initials: A
authors.lastname: Kanai
mesh_terms: D000368:Aged; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D003317:Corneal Dystrophies, Hereditary / Q000235:genetics*; D004252:DNA Mutational Analysis; D003941:Diagnostic Techniques, Ophthalmological; D016326:Extracellular Matrix Proteins; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000235:genetics*; D000099222:betaIG-H3 Protein
chemical_list: D016326:Extracellular Matrix Proteins; D009363:Neoplasm Proteins; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein