We report, for the first time, atypical granular corneal dystrophy type 2 with cornea guttata associated with a single R124H mutation in a Chinese family.
It is our intention to demonstrate that the pre-operative genetic screening for TGFBI mutations should be mandatory for refractive surgery candidates.Patients and MethodsIn this study, we reviewed the proband's post-LASIK slit-lamp and in vivo confocal microscopy images and genetic testing results, and performed genetic testing on eleven additional members of the family to investigate the penetrance of corneal dystrophy in asymptomatic members who carry the mutation.ResultsThe proband demonstrated a post-LASIK exacerbation of Granular Corneal Dystrophy type 2 (GCD2), identified as a TGFBI R124H mutation.
Screening for the TGF β-induced gene found the heterozygous p.R124H mutation associated with granular corneal dystrophy type 2 in each of the 4 individuals with corneal opacities as well as in a fifth individual who did not have any corneal opacities, for a prevalence of 0.24%.
One mutation, generating an arginine to histidine amino acid substitution at position 124 in mature TGFBIp leads to granular corneal dystrophy type 2 (GCD2).
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.
Granular corneal dystrophy type 2 (GCD2) is an autosomal dominant disease caused by a R124H point mutation in the transforming growth factor-β-induced gene (TGFBI).
We describe the phenotypic range of GCD2 heterozygotes for the common R124H mutation in TGFBI; seven with an extremely mild phenotype and six with an extremely severe phenotype.
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.
Primary culture corneal fibroblasts were isolated from the corneas of healthy subjects and patients with granular corneal dystrophy type 2 (GCD2) with a homozygous mutation in TGFBI R124H.
Genetic examination identified that two ACD subjects were associated with homozygous R124H mutation of TGFBI, and four LCD I subjects were all associated with R124C heterozygous mutation.
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.
Both granular and lattice deposits are present in Avellino corneal dystrophy (ACD), primarily associated with the R124H mutation of transforming growth factor-β-induced (TGFBIp).