title: Double mutation (R124H, N544S) of TGFBI in two sisters with combined expression of Avellino and lattice corneal dystrophies.
abstract: OBJECTIVE
  The R124H mutation of the keratoepithelin gene (TGFBI) causes Avellino corneal dystrophy whereas the N544S mutation of this same gene gives rise to lattice corneal dystrophy. We now report two cases with both R124H and N544S mutations of TGFBI.
  
  
  METHODS
  Genomic DNA and cDNA were isolated from the proband and family members and were subjected to polymerase chain reaction-mediated amplification of exons 1-17 of TGFBI. The amplification products were directly sequenced. Allele-specific cloning and sequencing were applied to evaluate the compound heterozygous mutation.
  
  
  RESULTS
  Molecular genetic analysis revealed that the proband and one sister harbored both a heterozygous CGC-->CAC (Arg-->His) mutation at codon 124 and a heterozygous AAT-->AGT (Asn-->Ser) mutation at codon 544 of TGFBI. Slit-lamp examination revealed multiple granular regions of opacity and lattice lines in the corneal stroma of the proband and her sister with the double mutation. Allele-specific cloning and sequencing revealed that the R124H and N544S mutations are on different chromosomes.
  
  
  CONCLUSIONS
  As far as we are aware, this is the first report of a patient with a double mutation (R124H, N544S) of TGFBI causing an autosomal dominant form of corneal dystrophy. The clinical manifestations of the two cases with both R124H and N544S mutations appeared to be a summation of Avellino and lattice corneal dystrophies.
authors.affiliation: Department of Ophthalmology, Yamaguchi University Graduate School of Medicine, Ube City, Yamaguchi, Japan. n.yamada@po.cc.yamaguchi-u.ac.jp
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Yamada
authors.forename: Koji
authors.initials: K
authors.lastname: Kawamoto
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Morishige
authors.forename: Tai-ichiro
authors.initials: T
authors.lastname: Chikama
authors.forename: Teruo
authors.initials: T
authors.lastname: Nishida
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Nishioka
authors.forename: Naoko
authors.initials: N
authors.lastname: Okayama
authors.forename: Yuji
authors.initials: Y
authors.lastname: Hinoda
mesh_terms: D000368:Aged; D003317:Corneal Dystrophies, Hereditary / Q000175:diagnosis / Q000235:genetics*; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D010641:Phenotype; D035781:Siblings; 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