A novel mutation of the TGFBI gene found in a Vietnamese family with atypical granular corneal dystrophy.

BACKGROUND Mutation of the human transforming growth factor beta-induced (TGFBI) gene causes granular corneal dystrophy (GCD) in various ethnic groups. In this report, we identify the genetic defect on the TGFBI gene in a Vietnamese family with atypical GCD . CASES The patient and her relatives were examined clinically. Genomic DNA was extracted from blood leukocytes. Fifty normal Vietnamese were used as controls. Analysis of the TGFBI gene was performed using polymerase chain reaction and direct sequencing. OBSERVATIONS The 42-year-old proband clinically showed multiple white dot-like opacities scattered in the anterior and mid-stroma of the central cornea. Unlike GCD, these deposits were smaller, localized deeper and less severe. DNA analysis revealed a nucleotide transversion at codon 123 (GAC --> CAC), causing Asp --> His substitution (D123H). This mutation was also detected in 3 out of 5 unaffected family members, but was absent in the 50 normal controls. CONCLUSIONS The novel D123H mutation of the TGFBI gene was not co-segregated with GCD in the family studied, and did not exist in the control population. It probably was a disease-causing mutation, thus expected to cause a novel variant of GCD in the proband. The detection of the D123H mutation in three unaffected family members indicates that it has low penetrance for GCD.