The TGFBI A546D mutation causes an atypical type of lattice corneal dystrophy

To report the clinical, molecular, and histopathological features of a distinct transforming growth factor-beta-induced (TGFBI) gene-linked amyloidotic corneal dystrophy exhibiting an unusual lattice pattern.

A complete ophthalmologic examination was performed in 10 individuals of a Mexican family in which autosomal dominant transmission of the disease was observed. DNA was obtained from peripheral blood leukocytes of each participating subject. Genetic analyses included TGFBI polymerase chain reaction (PCR) amplification and automated nucleotidic sequencing of exons 4, 11, 12, 13, and 14 from genomic DNA. Histological analysis of corneal tissue from an affected individual who underwent a penetrating keratoplasty was also performed.

The corneal phenotype in this pedigree was characterized by multiple bilateral round opacities in the central part of the cornea combined with a conspicuous central and peripheral lattice pattern. TGFBI analysis revealed a heterozygous point mutation at exon 12 (1637 C>A) in all affected individuals, predicting an A546D missense change.

The lattice phenotype resulting from the TGFBI A546D mutation in this family is distinct from that observed in a previously described pedigree carrying the A546D mutation and exhibiting a phenotype designated "polymorphic corneal amyloidosis". We propose this particular disorder to be classified as an atypical type of lattice stromal corneal dystrophy.