This study expands on our previous research investigating dystrophic stromal aggregates, with the aim of better elucidating the pathomechanism of two conditions arising from the most common TGFBI mutations: granular corneal dystrophy type 1 (GCD1; R555W) and lattice corneal dystrophy type 1 (LCD1; R124C).
The R124C mutation of the TGFBI gene gives rise to lattice corneal dystrophy type I, which is characterized by irregularity, turbulence, and opacity of the corneal epithelium.
Spontaneous mutations were detected in 2 families: an R124C mutation in 1 family with lattice corneal dystrophy (LCD) type I and an A546D mutation in the other with atypical LCD.
The fact that the 43-kDa protein fragment was present primarily in R124C and R124H but not in WT implicates its potential role in the protein deposits of LCD.
The novel mutations c.(1702G>C and 1706T>A; p.Arg514Pro and Phe515Leu), c. 531C>T (p. Arg124Cys), c.1876A>G (p.His572Arg) in TGFBI were responsible for LCD in the 3 families.
Genomic DNA was extracted from peripheral leukocytes from six affected and three unaffected members of a family with lattice corneal dystrophy type I. Exon 4 of the transforming growth factor-induced gene (TGFBI) was screened for the most frequent mutation, R124C, in the proband by sequencing.
We identified two TGFBI mutations: R124C (exon 4), which segregated with lattice type I corneal dystrophy, and R555W (exon 12), which segregated granular type I corneal dystrophy.
Although a slit-lamp examination showed features of LCDI in most cases, the age at onset of the symptoms was several years later than that in cases of LCDI with an R124C mutation.
Although a slit-lamp examination showed features of LCDI in most cases, the age at onset of the symptoms was several years later than that in cases of LCDI with an R124C mutation.
Two mutations in the TGFBI gene (A546D and P551Q) cosegregated with LCD in an extensively studied family that lacked the R124C mutation that frequently accompanies this form of corneal amyloidosis.
In exon 4, an R124H mutation associated with Avellino corneal dystrophy (ACD) was found in 39/44 families (86.4%) and an R124C mutation associated with lattice corneal dystrophy type 1 (LCD1) was detected in 2/44 families (4.5%).