TGFBI – Epithelial Basement Membrane Dystrophy

A minority of epithelial basement membrane dystrophy (EBMD) cases arise from autosomal dominant mutations in TGFBI, distinct from the typical degenerative process. In a UK cohort of 68 probands with TGFBI-related corneal dystrophies and 23 with bilateral EBMD, nine different TGFBI mutations were identified, with p.Gly623Asp observed in five unrelated individuals—two of whom presented with EBMD—indicating a rare genetic etiology for EBMD (5 probands) (PMID:27737463). Disease onset typically occurred in the fourth decade with recurrent corneal epithelial erosion and mild subepithelial opacities. Missense mutations cluster in fasciclin-4, and in vitro studies demonstrate that other TGFBI hotspot mutations (e.g., Arg124) enhance amyloid fibrillogenesis, suggesting a common amyloidogenic mechanism (PMID:12392546).

References

• Investigative ophthalmology & visual science • 2016 • Genotype-Phenotype Correlation for TGFBI Corneal Dystrophies Identifies p.(G623D) as a Novel Cause of Epithelial Basement Membrane Dystrophy. PMID:27737463
• European journal of biochemistry • 2002 • BIGH3 (TGFBI) Arg124 mutations influence the amyloid conversion of related peptides in vitro. PMID:12392546

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