Different phenotypes of lattice corneal dystrophy type I in patients with 417C>T (R124C) and 1762A>G (H572R) mutations in TGFBI (BIGH3)

PURPOSE: To describe clinical data and to characterize mutations in the transforming growth factor beta-induced (TGFBI) gene in patients from three unrelated Chilean families with lattice corneal dystrophy type I (LCDI). METHODS: Snellen acuity tests, anterior segment slit lamp examinations, dilated fundus evaluations, and tonometry were performed for seven patients—five females and two males belonging to three unrelated families—affected with lattice corneal dystrophy Type I. Genomic DNA was also extracted from peripheral leukocytes from the seven patients and four healthy relatives. The 417C>T mutation (R124C) was screened using PCR-RFLP for the seven patients and four healthy relatives. Exons 11, 12, 13, and 14 were sequenced in one patient not carrying the mutation in codon 124. Comparison of phenotype to genotype was performed. RESULTS: The seven patients studied exhibited LCDI in both eyes, most of which were symmetric. Affected individuals demonstrated progression from central subepithelial needlelike deposits and polymorphic anterior stromal opacities. The age at onset of symptoms varied between six to 15 years old in Family One; the patient in Family Two was five years old and the patient in Family Three was 21 years old. Visual acuity varied from 1.0 to 0.05. Two patients, aged 50 and 45 years, underwent penetrating keratoplasty in both eyes, and two patients, aged 47 and 24 years, underwent penetrating keratoplasty in one eye. The only patient in Family Three exhibited a somewhat distinct phenotype, with yellowish discoloration in the anterior stroma and fewer, but thicker lattice lines than the patients in Families One and Two. Screening for the mutation C>T at the nucleotide position 417 (R124C) in exon 4 in the three families revealed the heterozygous R124C mutation in Families One and Two. In Family Two, the mutation was a de novo mutation, as neither parent was a carrier. Screening by sequencing analysis for mutation in exons 11, 12, 13, and 14 in the affected patient in Family Three revealed a heterozygous A1762G mutation (H572R) in exon 13. CONCLUSIONS: This is the second report of the 417C>T mutation and the first report of 1762 A>G mutation (H572R) in Chilean patients. The H572R mutation identified is associated with a distinct lattice corneal dystrophy type I phenotype.