title: TGFBI gene mutations causing lattice and granular corneal dystrophies in Indian patients.
abstract: OBJECTIVE
  To identify mutations in the TGFBI gene in Indian patients with lattice corneal dystrophy (LCD) or granular corneal dystrophy (GCD) and to look for genotype-phenotype correlations.
  
  
  METHODS
  Thirty-seven unrelated patients were studied, 18 with LCD and 19 with GCD. The diagnosis of LCD or GCD was made on the basis of clinical and/or histopathological evaluation. Exons and flanking intron sequences of the TGFBI gene were amplified by PCR with specific primers. PCR products were screened by the method of single-strand conformation polymorphism followed by sequencing. Mutations were confirmed by screening at least 100 unrelated normal control subjects.
  
  
  RESULTS
  Mutations were identified in 14 of 18 patients with LCD and in all 19 patients with GCD. In LCD, three novel heterozygous mutations found were glycine-594-valine (Gly594Val) in 2 of 18 patients, valine-539-aspartic acid (Val539Asp) in 1 patient, and deletion of valine 624, valine 625 (Val624-Val625del) in 1 patient. In addition, mutation of arginine 124-to-cysteine (Arg124Cys) was found in 8 of 18 patients and histidine 626-to-arginine (His626Arg) in 2 of 18 patients. Atypical clinical features for LCD were noted in patients with the Gly594Val and Val624-Val625del mutations. In GCD, 18 patients with GCD type I had a mutation of arginine 555-to-tryptophan (Arg555Trp) and 1 patient with GCD type III (Reis-Bucklers dystrophy), had the Arg124Leu mutation. Seven novel single-nucleotide polymorphisms (SNPs) were also found, of which a change of leucine 269 to phenylalanine (Leu269Phe) was found in 12 of 18 patients with the Arg555Trp mutation.
  
  
  CONCLUSIONS
  Arg124Cys and Arg555Trp appear to be the predominant mutations causing LCD and GCD, respectively, in the population studied. The novel mutations identified in this study are associated with distinct phenotypes.
authors.affiliation: Kallam Anji Reddy Molecular Genetics Laboratory, L.V. Prasad Eye Institute, Hyderabad, India.
authors.forename: S V V Kalyana
authors.initials: SV
authors.lastname: Chakravarthi
authors.forename: Chitra
authors.initials: C
authors.lastname: Kannabiran
authors.forename: Mittanamalli S
authors.initials: MS
authors.lastname: Sridhar
authors.forename: Geeta K
authors.initials: GK
authors.lastname: Vemuganti
mesh_terms: D000328:Adult; D003317:Corneal Dystrophies, Hereditary / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D017931:DNA Primers; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D016212:Transforming Growth Factor beta / Q000235:genetics*; D000099222:betaIG-H3 Protein
chemical_list: D017931:DNA Primers; D016326:Extracellular Matrix Proteins; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein