Novel TACSTD2 gene Nonsense Mutation in a Family with Gelatinous Drop-Like Corneal Dystrophy (GDLD)

Abstract

Purpose: Gelatinous drop-like corneal dystrophy (GDLD, OMIM #204870) is a rare autosomal recessive corneal disorder, most often found in Japanese population. GDLD is caused by mutations in TACSTD2, a gene located at chromosome 1p32. The purpose of this study is to describe the results of clinical assessment and molecular analysis for TACSTD2 gene in a Mexican family affected with GDLD.

Methods: A Mexican family with 4 affected and 1 healthy subject was studied. Each patient underwent complete ophthalmological and OCT (optical coherence tomography) analysis, and B-Scan. Molecular analysis consisted in genomic DNA extraction. Amplification of TACSTD2 coding region by PCR and automatized direct nucleotide sequencing all samples were analyzed.

Results: A consanguineous Mexican family affected in 2 generations, with no evidence of associated systemic disorders or mental retardation suggesting a syndromic entity was studied. All the affected subjects presented poor vision, photophobia and foreign body sensation. Clinical examination showed subepithelial deposits with yellow-whitish nodular lesions in mulberry-like pattern. Corneal opacities involving the visual axis as well as stromal and subepithelial vascularization were observed. Molecular analysis showed a TACSTD2 gene homozygous mutation c.331G> T, which predicts a p.E111X a nonsense mutation. This mutation was demonstrated in DNA from all affected patients. Genetic analysis indicated that the healthy sib is heterozygous for the p.E111X mutation. Penetrating keratoplasty was simultaneously performed in 3 patients successfully.

Conclusions: This is the first report of the clinical and genetic characteristics of Mexican patients with Gelatinous Drop-Like Corneal Dystrophy, The identified mutation p.E111X in TACSTD2 gene in this family is a novel mutation. Our results expand the mutational spectrum in TACSTD for GDLD.