To identify the types of <i>TGFBI</i> (transforming growth factor, beta-induced) gene mutations in three Chinese families with Reis-Bücklers corneal dystrophy (RBCD), lattice corneal dystrophy type I (LCDI), or Avellino corneal dystrophy (ACD) and to investigate the relationship between the phenotypes and genotypes of corneal dystrophy.
In this study, patients with macular corneal dystrophy (MCD; n = 18), granular corneal dystrophy type 1 (GCD1; n = 12), and lattice corneal dystrophy type 1 (LCD1; n = 4), as well as 50 healthy controls, were subjected to clinical and genetic examinations.
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).
Silencing of exogenous TGFBI was observed at mRNA and protein levels, and in an ex vivo model of LCDI with an efficient suppression of the endogenous mutant allele.
In this study, we investigated whether the phenotypic difference observed between two lattice corneal dystrophy type 1 (LCD type 1) cases caused by either a single A546D substitution or an A546D/P551Q double substitution in TGFBIp (transforming growth factor beta induced protein) can be ascribed to (i) a difference in the proteomes of corneal amyloid deposits, (ii) altered proteolysis of TGFBIp, or (iii) structural changes of TGFBIp introduced by the P551Q amino acid substitution.
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.
Different types of granular corneal dystrophy (GCD) and lattice corneal dystrophy (LCD) are associated with mutations in the transforming growth factor beta induced gene (TGFBI).
In our study, thirty patients from five pedigrees and ten sporadic patients were diagnosed as four TGFBI gene-linked corneal dystrophies of granular corneal dystrophy type I (GGCD I), Avellino corneal dystrophy (ACD), lattice corneal dystrophy type I (LCD I), and lattice corneal dystrophy type IIIA (LCD IIIA), and in total, seven disease-causing mutations, namely R555W, A546D, A546T, and T538P mutations in exon 12, R124H and R124C mutations in exon 4, and P501T mutation in exon 11, were identified, while four polymorphisms of V327V, L472L, F540F, and 1665-1666insC were screened in exons 8, 11, and 12.
Specific components of transforming growth factor-beta-induced protein (TGFBIp) responsible for amyloid deposits in lattice corneal dystrophy (LCD) have not been delineated.
As with other corneal dystrophies, this LCD subtype is also caused by a mutation (p. Leu527Arg) of the transforming growth factor, beta-induced (TGFBI) gene.
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.
The purpose of this study was to report the association of phenotypic features characteristic of lattice corneal dystrophy (LCD) with a monoclonal gammopathy of undetermined significance (MGUS) after exclusion of a coding region mutation in transforming growth factor beta-induced (TGFBI) gene.