Evaluation of genotype-phenotype associations in leber congenital amaurosis

Retina. Oct-Nov 2005;25(7):919-29. doi: 10.1097/00006982-200510000-00016.


Purpose: To describe the clinical phenotypes associated with various genotypes known to cause Leber congenital amaurosis (LCA).

Methods: One hundred ten LCA patients were screened for various probable disease-causing gene sequence variations. Those patients with a probable disease-causing sequence variation in one of six genotypes were recalled for a follow-up examination. Evaluations included assessment of visual acuity, slit-lamp biomicroscopy, and dilated fundus examination. When possible, Goldmann perimetry was also performed.

Results: Of the 37 LCA patients with suspected disease-causing sequence variations, 7 had an AIPL1 variation, 8, a CRB1 variation, 2, a CRX variation, 4, a GUCY2D variation, 11, an RPE65 variation, and 5, an RPGRIP1 variation. Across the 6 genotypes, we observed a wide range of visual acuities from 20/40 to no light perception. The widest range of vision was noted for patients with a CRB1 or RPE65 variation. Younger patients with an AIPL1 or RPGRIP1 variation were found to have severely reduced vision. Drusenlike deposits were more selectively observed in patients with mutations in the AIPL1, CRB1, RPE65, and RPGRIP1 genes, whereas focal regions of peripheral chorioretinal atrophy were observed only in patients with AIPL1 or RPE65 variations. Neurologic, intellectual, or psychomotor developmental delay was noted in 8.1% of our cohort.

Conclusions: There was considerable overlap of phenotypic expression in six genetic subtypes in our LCA cohort. However, phenotypic trends were noted in our patients' visual acuities and posterior segment findings within genotypes. These findings have practical value for genetic screening strategies for LCA patients based upon phenotype as well as for counseling patients on their visual prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adolescent
  • Adult
  • Aged
  • Blindness / congenital
  • Blindness / genetics*
  • Carrier Proteins / genetics*
  • Child
  • Child, Preschool
  • Eye Proteins / genetics*
  • Female
  • Genetic Variation
  • Genotype
  • Guanylate Cyclase / genetics*
  • Homeodomain Proteins / genetics*
  • Humans
  • Male
  • Membrane Proteins / genetics*
  • Middle Aged
  • Nerve Tissue Proteins / genetics*
  • Phenotype
  • Proteins / genetics*
  • Receptors, Cell Surface / genetics*
  • Sequence Analysis, DNA
  • Trans-Activators / genetics*
  • cis-trans-Isomerases


  • AIPL1 protein, human
  • Adaptor Proteins, Signal Transducing
  • CRB1 protein, human
  • Carrier Proteins
  • Eye Proteins
  • Homeodomain Proteins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Proteins
  • RPGRIP1 protein, human
  • Receptors, Cell Surface
  • Trans-Activators
  • cone rod homeobox protein
  • guanylate cyclase 1
  • retinoid isomerohydrolase
  • Guanylate Cyclase
  • cis-trans-Isomerases