TGFBI gene mutations in Hungary – polymorphic corneal amyloidosis caused by the novel F547S mutation

Abstract

Abstract Purpose To identify mutations in the Transforming Growth Factor Beta Induced (TGFBI) gene in Hungarian patients with corneal dystrophy and to characterize their histological features. Methods Exons of TGFBI gene were sequenced in 38 members of 15 unrelated families with corneal dystrophy. Exon 12 was sequenced in 100 healthy controls. Immunohistological analysis of corneal buttons excised during penetrating keratoplasty was performed. Results Molecular genetic analysis revealed a heterozygous R124C mutation in 18 patients with lattice type I dystrophy. A R555W heterozygous mutation was detected in five patients with granular Groenouw type I corneal dystrophy and the R555Q heterozygous mutation was found in four patients clinically diagnosed with Reis‐Bücklers (one patient) and Thiel‐Behnke (three patients) dystrophy. Three patients with “atypical granular” dystrophy later diagnosed as Avellino dystrophy were heterozygous for the R124H mutation. No other than the novel heterozygous T1640C mutation causing the F547S amino acid exchange was detected in a patient with polymorphic corneal amyloidosis. The mutation could not be found in healthy controls. Immunohistochemistry showed the presence of BIGH3 protein deposits in all examined corneal buttons. Electron microscopy confirmed the presence of amyloid fibrils in the case of the novel mutation. Conclusion Our results indicate that molecular genetic analysis is required to confirm the diagnosis of corneal dystrophies. We report the first cases of Avellino dystrophy from Central‐Eastern Europe. The novel F547S mutation causes polymorphic corneal amyloidosis.