title: Genotype-phenotype correlation in 2 Indian families with severe granular corneal dystrophy.
abstract: OBJECTIVE
  To determine genotypes in 2 Indian families with severe granular corneal dystrophy, to document clinical and histopathologic features, and to attempt a genotype-phenotype correlation.
  
  
  METHODS
  Mutation analysis of exon 12 of the TGFBI gene was carried out in 9 individuals from 2 families.
  
  
  RESULTS
  A C-->T mutation at residue 1710 of TGFBI complementary DNA, corresponding to an Arg555Trp mutation in keratoepithelin, was found in affected members of both families. In 5 patients, this mutation was homozygous, and it was heterozygous in the other 4. Clinical examination revealed a severe form of granular corneal dystrophy with early onset and superficial lesions in the homozygous individuals and a milder phenotype in the heterozygous individuals. Histopathologic evaluation of corneal specimens from 2 homozygous patients confirmed the presence of superficial granular deposits.
  
  
  CONCLUSIONS
  To our knowledge, this is the first molecular and clinical characterization of severe granular corneal dystrophy in India. Genotype-phenotype correlation and comparison with earlier reports on this entity highlight the uniform expressivity of the Arg555Trp allele in homozygous individuals.
  
  
  CONCLUSIONS
  Homozygous granular corneal dystrophy has a severe phenotype and can be recognized based on clinical and histopathologic features, especially in association with consanguinity or inbreeding.
authors.affiliation: Kallam Anji Reddy Molecular Genetics Laboratory and Ophthalmic Pathology Service, Professor Brien Holden Eye Research Centre, L. V. Prasad Eye Institute, L.V. Prasad Marg, Banjara Hills, Hyderabad 500-034, India. chitra@lvpei.org
authors.forename: Chitra
authors.initials: C
authors.lastname: Kannabiran
authors.forename: Mittanamalli S
authors.initials: MS
authors.lastname: Sridhar
authors.forename: S Kalyana
authors.initials: SK
authors.lastname: Chakravarthi
authors.forename: Geeta K
authors.initials: GK
authors.lastname: Vemuganti
authors.forename: Meena
authors.initials: M
authors.lastname: Lakshmipathi
mesh_terms: D000293:Adolescent; D000328:Adult; D003241:Consanguinity; D003317:Corneal Dystrophies, Hereditary / Q000175:diagnosis* / Q000235:genetics*; D003319:Corneal Stroma / Q000473:pathology*; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005190:Family; D005260:Female; D005838:Genotype; D006801:Humans; D007194:India; D008297:Male; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation; D016133:Polymerase Chain Reaction; 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