Phenotype-Genotype Correlations of TGFBI in Asian Patients

Abstract

Purpose: : Phenotypic-genotype correlations of mutations in Tissue Growth factor beta-inducible (TGFBI) responsive gene in Asian patients with Bowman’s membrane and stromal corneal dystrophies.

Methods: : Twenty unrelated families with Bowman’s membrane and stromal corneal dystrophies presenting to a tertiary referral centre underwent visual acuity testing, and ocular examination with slit lamp biomicroscopy. Blood was collected for genetic analysis and all 17 exons and flanking intron sequences of the TGFBI gene were sequenced.

Results: : There were 10 males and 10 females in this series, with 10 Chinese, 4 Malays, 4 Indians and 2 Indonesians. The mean age was 48.9 years (range 9 -72). Five (out of 9) patients with granular dystrophy had the R555W mutation, while the other 4 had the R124H mutation. Of the 9 patients with lattice dystrophy, 2 had the H626R mutation and 1 had the H572R, while the remaining 5 had the R124C mutation. One novel mutation A620D in a patient with lattice dystrophy was identified. The residue A620 shows high interspecies conservation indicating likely pathogenicity with mutations at this site. Other mutations detected include R124L and R555Q in 2 Reis- Buckler dystrophy patients and H572R. There was marked phenotypic variation amongst different TGFBI mutations.

Conclusions: : The most common mutation amongst our patients was R555W and R124C. We describe the clinical features of a previously unreported TGFBI mutation. There was marked phenotypic variability in TGFBI mutations in Asian patients.

Keywords: cornea: basic science • genetics • cornea: stroma and keratocytes