title: TGFBI (BIGH3) gene mutations in Hungary--report of the novel F547S mutation associated with polymorphic corneal amyloidosis.
abstract: OBJECTIVE
  To identify mutations in the Transforming Growth Factor Beta Induced (TGFBI) gene in Hungarian patients with corneal dystrophy and to characterize histological features of their corneal buttons excised during penetrating keratoplasty.
  
  
  METHODS
  Exons of TGFBI were sequenced in 38 members of 15 unrelated families with corneal dystrophy and exon 12 was also sequenced in 100 healthy controls from the same population. Immunohistological analysis of available corneal buttons excised during penetrating keratoplasty was also 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 a 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. A novel heterozygous mutation (T1640C) causing a F547S amino acid exchange was detected in a patient with polymorphic corneal amyloidosis. 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.
  
  
  CONCLUSIONS
  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. We conclude that the novel F547S mutation causes polymorphic corneal amyloidosis since no other mutations were detected in the TGFBI gene of this patient and the novel mutation could not be found in healthy controls.
authors.affiliation: Department of Ophthalmology, University of Debrecen, Medical and Health Science Center, Debrecen, Hungary. ltakacs@dote.hu
authors.forename: Lili
authors.initials: L
authors.lastname: Takács
authors.forename: Gergely
authors.initials: G
authors.lastname: Losonczy
authors.forename: Klára
authors.initials: K
authors.lastname: Matesz
authors.forename: István
authors.initials: I
authors.lastname: Balogh
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Sohajda
authors.forename: Károly
authors.initials: K
authors.lastname: Tóth
authors.forename: Ferenc
authors.initials: F
authors.lastname: Fazakas
authors.forename: György
authors.initials: G
authors.lastname: Vereb
authors.forename: András
authors.initials: A
authors.lastname: Berta
mesh_terms: D019943:Amino Acid Substitution; D000686:Amyloidosis / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D001483:Base Sequence; D003315:Cornea / Q000473:pathology; D003317:Corneal Dystrophies, Hereditary / Q000145:classification / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D006814:Hungary; D015948:Keratoplasty, Penetrating; D008875:Middle Aged; D009154:Mutation; D010649:Phenylalanine; D012694:Serine; D016212:Transforming Growth Factor beta / Q000235:genetics*; D000099222:betaIG-H3 Protein
chemical_list: D016326:Extracellular Matrix Proteins; D010649:Phenylalanine; D012694:Serine; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein