Genetic and phenotypic investigation of a Chinese pedigree with lattice corneal dystrophy IIIB subtype.

PURPOSE: To investigate phenotypes and disease-causing mutation in the transforming growth factor b-induced gene (TGFBI) in a Southern Chinese pedigree with lattice corneal dystrophy (LCD) IIIB with complicated cataract.

METHODS

A Southern Chinese pedigree with lattice corneal dystrophy IIIB with complicated cataract was recruited. Comprehensive ophthalmic investigations were performed before and after cataract surgery of phacoemulsification and intraocular lens implantation in the proband's both eyes. Peripheral blood was collected from the proband, and genomic DNA was extracted. All exons of the TGFBI gene were sequenced to screen possible mutations.

RESULTS

A bilateral LCD IIIB subtype was observed in the proband. Optical coherence tomography further revealed superreflective changes in the subepithelial and stroma layers of the cornea, with reduced central corneal thickness. Notably, bilateral cataract was found in the proband. Direct sequencing detected a recurrent heterozygous missense c.1877A > G mutation in exon 14 of the TGFBI gene, resulting in substitution of histidine with arginine (p.H626R).

CONCLUSION

The current study was the first report of the TGFBI p.H626R mutation in Southern Chinese, suggesting that it could be a mutation hotspot across populations. Moreover, the mutation was associated with LCD IIIB subtype with complicated cataract, which had not been reported before, pointing to clinical heterogeneity of the mutation.