title: Correlations of genotype with phenotype in Indian patients with primary congenital glaucoma.
abstract: OBJECTIVE
  To establish the genotype-phenotype correlations of various CYP1B1 (human cytochrome P450) mutations in patients in India with primary congenital glaucoma (PCG).
  
  
  METHODS
  The study cohort comprised 146 patients with PCG from 138 pedigrees. Patients were analyzed for six distinct CYP1B1 mutations by sequencing and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. A severity index for grading various PCG phenotypes was constructed based on clinical parameters.
  
  
  RESULTS
  Six mutations were identified in 45 patients analyzed and genotype-phenotype correlations were established for 43 of them. The percentages of severe phenotypes associated with various mutations in at least one eye were: frameshift, 100%; G61E, 66.7%; P193L, 62.5%; E229K, 80%; R368H, 72%; R390C, 83.3%. The frameshift mutation resulted in blindness. Based on the severity index, the disease severity was graded from normal to severe and the prognosis from good to very poor (blind). De novo mutation was identified in one family.
  
  
  CONCLUSIONS
  This is the first study to attempt to devise a severity index for grading various PCG phenotypes and to use genotype as an indicator to predict the prognoses of the disorder. This index may help guide therapy and counseling of the afflicted family regarding the progression of the disorder. All patients with severe phenotypes showed poor prognoses (r = 0.976; P < 0.0001). The data derived from this study could be used as an added clinical tool in disease management. Integrated management of PCG that makes use of a genetic approach could yield better results than medical, surgical, and rehabilitation interventions alone.
authors.affiliation: Kallam Anji Reddy Molecular Genetics Laboratory, Brien Holden Eye Research Centre, Hyderabad Eye Research Foundation, Hyderabad, India.
authors.forename: Shirly G
authors.initials: SG
authors.lastname: Panicker
authors.forename: Anil K
authors.initials: AK
authors.lastname: Mandal
authors.forename: Aramati B M
authors.initials: AB
authors.lastname: Reddy
authors.forename: Vijaya K
authors.initials: VK
authors.lastname: Gothwal
authors.forename: Seyed E
authors.initials: SE
authors.lastname: Hasnain
mesh_terms: D000328:Adult; D017668:Age of Onset; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D002675:Child, Preschool; D065633:Cytochrome P-450 CYP1B1; D004252:DNA Mutational Analysis; D005838:Genotype; D005901:Glaucoma / Q000145:classification / Q000151:congenital* / Q000235:genetics*; D006801:Humans; D007194:India; D007223:Infant; D007231:Infant, Newborn; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1