Mutational analysis and clinical correlation in Leber congenital amaurosis

Ophthalmic Genet. 2000 Sep;21(3):135-50.


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).

Purpose: 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.

MeSH terms

  • Adult
  • Blindness / congenital
  • Blindness / diagnosis
  • Blindness / genetics*
  • Carrier Proteins
  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • Eye Proteins / genetics*
  • Female
  • Follow-Up Studies
  • Genotype
  • Guanylate Cyclase / genetics*
  • Homeodomain Proteins / genetics*
  • Humans
  • Infant
  • Male
  • Mutation / genetics*
  • Optic Atrophies, Hereditary / diagnosis
  • Optic Atrophies, Hereditary / genetics*
  • Pedigree
  • Phenotype
  • Polymerase Chain Reaction
  • Polymorphism, Single-Stranded Conformational
  • Proteins / genetics*
  • Trans-Activators / genetics*
  • cis-trans-Isomerases


  • Carrier Proteins
  • Eye Proteins
  • Homeodomain Proteins
  • Proteins
  • Trans-Activators
  • cone rod homeobox protein
  • retinoid isomerohydrolase
  • Guanylate Cyclase
  • cis-trans-Isomerases