title: Phenotype-genotype correlations in patients with TGFBI-linked corneal dystrophies in Taiwan.
abstract: OBJECTIVE
  To determine the phenotype-genotype correlations in patients with corneal dystrophies associated with human transforming growth factor-β-induced (TGFBI) mutations at the National Taiwan University Hospital.
  
  
  METHODS
  Twenty-five affected patients from 15 families with corneal dystrophies were recruited. They underwent slit-lamp biomicroscopy and visual acuity examinations. Genomic DNA was extracted from their peripheral blood, and the exons amplified from TGFBI were sequenced.
  
  
  RESULTS
  Eleven patients from 9 families with granular corneal dystrophy (GCD) presented with a wide spectrum of dot or fleck opacities and shared some similar clinical features. Genetic studies revealed an R124H mutation in 5 families and an R555W mutation in 4 families. A patient with GCD type 2 and an R124H mutation showed a marked increase in opacities in the laser-assisted in situ keratomileusis (LASIK) flap interface. Six patients from 3 families with superficial honeycomb opacities had an R555Q mutation. Of the 4 patients from 3 families with variant lattice line opacities, 3 from 2 families had an R124C mutation, whereas 1 from the third family had an A546D mutation. Spontaneous mutations were detected in 2 families: an R124C mutation in 1 family with lattice corneal dystrophy (LCD) type I and an A546D mutation in the other with atypical LCD.
  
  
  CONCLUSIONS
  In most cases, TGFBI-linked corneal dystrophies had good phenotype-genotype correlations; however, some phenotypic variation was present. The most common mutations in Taiwan were R124H in GCD type 2 and R555W in GCD type 1. The R555Q mutation in Thiel-Behnke corneal dystrophy is not as rare in Taiwan as it is in other Asian countries. Sequencing of TGFBI can aid in the precise classification of these corneal dystrophies.
authors.affiliation: Department of Ophthalmology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan. ychou51@ntu.edu.tw
authors.forename: Yu-Chih
authors.initials: YC
authors.lastname: Hou
authors.forename: I-Jong
authors.initials: IJ
authors.lastname: Wang
authors.forename: Cheng-Hsiang
authors.initials: CH
authors.lastname: Hsiao
authors.forename: Wei-Li
authors.initials: WL
authors.lastname: Chen
authors.forename: Fung-Rong
authors.initials: FR
authors.lastname: Hu
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D001483:Base Sequence; D002648:Child; D003317:Corneal Dystrophies, Hereditary / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D010375:Pedigree; D013624:Taiwan; D016212:Transforming Growth Factor beta / Q000235:genetics*; D000099222:betaIG-H3 Protein
chemical_list: D016326:Extracellular Matrix Proteins; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein