Expanding the mutational spectrum in TGFBI-linked cornealdystrophies: Identification of a novel and unusual mutation (Val113Ile)in a family with granular dystrophy

[摘要] Purpose: To report the clinical and molecular study of a family withan autosomal dominant stromal granular dystrophy of the cornea caused bya novel and unusual TGFBI gene mutation.Methods: A complete ophthalmological examination, corneal dystrophyphenotype characterization, PCR amplification, and automated nucleotidicsequencing of exons 4, 11,12, 13, and 14 of the TGFBI gene wascarried out on the family. DNA from 40 unrelated ethnically matchedhealthy individuals were analyzed as controls.Results: Corneal dystrophy in two sisters was characterized bymultiple grayish-white lesions located in the anterior and mid-stroma.Numerous small sized non-coalescent opacities were observed in theperipheral cornea while fewer larger lesions were apparent towards thecentral part of the cornea. A heterozygous missense mutation, consistingof a G to A transition at nucleotide position 384 in TGFBI exon 4that predicts a valine (GTT) to isoleucine (ATT) replacement in residue113 (Val113Ile) of the TGFBI protein was identified.Conclusions: This is the most 5' located mutation detected so far insubjects with TGFBI-linked corneal dystrophy. Valine 113 is strictlyconserved in TGFBI from several species and we suggest that thephenotype observed in these patients is related to the unusual locationof the mutation. Our results expand the mutational spectrum in the groupof TGFBI-linked corneal dystrophies.

[学科分类] 生物化学/生物物理