title: Mutational analysis and clinical correlation in Leber congenital amaurosis.
abstract: Leber congenital amaurosis (LCA, MIM 204001) is a clinically and genetically heterogeneous retinal disorder characterized by severe visual loss from birth, nystagmus, poor pupillary reflexes, retinal pigmentary or atrophic changes, and a markedly diminished electroretinogram (ERG).
  
  
  OBJECTIVE
  To examine 100 consecutive patients with LCA in order to assess the relative burden of the three known genes involved in LCA, namely retinal guanylyl cyclase (GUCY2D), retinal pigment epithelium protein ( RPE65), and the cone-rod homeobox (CRX), and to define their clinical correlates.
  
  
  METHODS
  Mutational analysis and detailed clinical examinations were performed in patients diagnosed with LCA at the Johns Hopkins Center for Hereditary Eye Diseases and the Montreal Children's Hospital.
  
  
  RESULTS
  Mutations were identified in 11% of our patients: GUCY2D mutations accounted for 6%, while RPE65 and CRX gene mutations accounted for 3% and 2%, respectively. The clinical presentation was variable; however, the visual evolution in patients with mutations in GUCY2D and CRX remained stable, while individuals with mutations in the RPE65 gene showed progressive visual loss.
  
  
  CONCLUSIONS
  This study suggests that molecular diagnosis of Leber congenital amaurosis could provide important information concerning prognosis and course of treatment.
authors.affiliation: Wilmer Eye Institute, The Johns Hopkins Center for Hereditary Eye Diseases, Baltimore, Maryland, USA. sdharmaraj@jhmi.edu
authors.forename: S R
authors.initials: SR
authors.lastname: Dharmaraj
authors.forename: E R
authors.initials: ER
authors.lastname: Silva
authors.forename: A L
authors.initials: AL
authors.lastname: Pina
authors.forename: Y Y
authors.initials: YY
authors.lastname: Li
authors.forename: J M
authors.initials: JM
authors.lastname: Yang
authors.forename: C R
authors.initials: CR
authors.lastname: Carter
authors.forename: M K
authors.initials: MK
authors.lastname: Loyer
authors.forename: H K
authors.initials: HK
authors.lastname: El-Hilali
authors.forename: E K
authors.initials: EK
authors.lastname: Traboulsi
authors.forename: O K
authors.initials: OK
authors.lastname: Sundin
authors.forename: D K
authors.initials: DK
authors.lastname: Zhu
authors.forename: R K
authors.initials: RK
authors.lastname: Koenekoop
authors.forename: I H
authors.initials: IH
authors.lastname: Maumenee
mesh_terms: D000328:Adult; D001766:Blindness / Q000151:congenital / Q000175:diagnosis / Q000235:genetics*; D002352:Carrier Proteins; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006162:Guanylate Cyclase / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation / Q000235:genetics*; D015418:Optic Atrophies, Hereditary / Q000175:diagnosis / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011506:Proteins / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics*; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase
chemical_list: D002352:Carrier Proteins; D005136:Eye Proteins; D006162:Guanylate Cyclase; D018398:Homeodomain Proteins; D011506:Proteins; D015534:Trans-Activators; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase; C109288:cone rod homeobox protein