Transforming growth factor beta-induced protein R124H mutant messenger RNA (TGFBI R124H mRNA)

Transforming growth factor beta-induced protein (TGFBI) R124H mutant mRNA is the transcript produced by a specific point mutation (CGC to CAC) in the TGFBI gene, which encodes the protein kerato-epithelin. In healthy individuals, the TGFBI protein is secreted into the extracellular matrix of the cornea where it mediates cell adhesion and collagen binding. However, the R124H mutation leads to the production of a misfolded protein that aggregates into amyloid and hyaline deposits within the corneal stroma, causing Granular Corneal Dystrophy Type 2 (GCD2), also known as Avellino corneal dystrophy. This condition results in progressive visual impairment and is exacerbated by corneal trauma or refractive surgery. As a therapeutic target, the R124H mutant mRNA is approached using allele-specific silencing techniques such as small interfering RNA (siRNA) or antisense oligonucleotides (ASOs). These therapies are designed to selectively recognize the single nucleotide polymorphism (SNP) of the mutant transcript, triggering its degradation while leaving the wild-type mRNA intact to maintain normal corneal function. By reducing the pool of mutant mRNA, these interventions aim to decrease the synthesis and subsequent accumulation of the pathogenic protein, potentially halting or reversing the progression of corneal opacification. Current research focuses on optimizing the specificity of these nucleic acid drugs and developing effective topical or intrastromal delivery systems.

Other names

BIGH3 R124H mRNAKerato-epithelin R124H mRNATGFBI Arg124His mRNATransforming growth factor-beta-induced gene clone 3 R124H mRNA

Allele-specific RNA interference (RNAi) or antisense oligonucleotide-mediated degradation of mutant mRNA to prevent the translation of toxic misfolded proteins.