The phenotype of arg555trp mutation in a large Turkish family with corneal granular dystrophy.
OBJECTIVE
A large Turkish family with 52 members, 26 of whom had Groenouw type 1 corneal granular dystrophy was evaluated by genetic linkage studies and mutation analyses. Phenotype-genotype correlations were also assessed.


METHODS
DNA from peripheral blood lymphocytes of 22 family members was used in establishing linkage to chromosome 5q31. Single-strand conformation polymorphism analysis was done to detect mutations in exons 4 and 12 of the human transforming growth factor beta-induced gene located on chromosome 5q31. Automated sequencing was performed on exon 12 of an affected patient.


RESULTS
Patients yonger than 15 years of age had typical linear, granular opacities whereas adults had coarser, deeper granular stromal deposits. These changes were not associated with recurrent erosions or significant visual disabilities. The family was linked to chromosome 5q31 and a DNA shift was observed on exon 12 of affected patients. CGG to TGG transition producing R555W mutation was found.


CONCLUSIONS
Segregation of Arg555Trp has been described as causing Groenouw type I corneal dystrophy of variable severity in patients of various ethnic backgrounds. In this large Turkish pedigree, the Arg555Trp mutation was associated with a mild phenotype that became clinically evident at five years of age but which remained asymptomatic in terms of corneal erosions.
Kiratli
H
H
Department of Ophthalmology, School of Medicine, Hacettepe University, Ankara, Turkey. hayyamk@ttnet.net.tr
Irkeç
M
M
Ozgül
K
K
Ogüş
A
A
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D003317:Corneal Dystrophies, Hereditary / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D016326:Extracellular Matrix Proteins; D005260:Female; D008040:Genetic Linkage; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D009363:Neoplasm Proteins / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D016212:Transforming Growth Factor beta / Q000235:genetics; D014421:Turkey; D000099222:betaIG-H3 Protein
D016326:Extracellular Matrix Proteins; D009363:Neoplasm Proteins; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein