The phenotype of Leber congenital amaurosis in patients with AIPL1 mutations

Arch Ophthalmol. 2004 Jul;122(7):1029-37. doi: 10.1001/archopht.122.7.1029.


Objectives: To describe the phenotype of Leber congenital amaurosis (LCA) in 26 probands with mutations in aryl hydrocarbon receptor interacting protein-like 1 protein (AIPL1) and compare it with phenotypes of other LCA-related genes. To describe the electroretinogram (ERG) in heterozygote carriers.

Methods: Patients with AIPL1-related LCA were identified in a cohort of 303 patients with LCA by polymerase chain reaction single-strand confirmational polymorphism mutation screening and/or direct sequencing. Phenotypic characterization included clinical and ERG evaluation. Seven heterozygous carrier parents also underwent ERG testing.

Results: Seventeen homozygotes and 9 compound heterozygotes were identified. The W278X mutation was most frequent (48% of alleles). Visual acuities ranged from light perception to 20/400. Variable retinal appearances, ranging from near normal to varying degrees of chorioretinal atrophy and intraretinal pigment migration, were noted. Atrophic and/or pigmentary macular changes were present in 16 (80%) of 20 probands. Keratoconus and cataracts were identified in 5 (26%) of 19 patients, all of whom were homozygotes. The ERG of a parent heterozygote carrier revealed significantly reduced rod function, while ERGs for 6 other carrier parents were normal.

Conclusions: The phenotype of LCA in patients with AIPL1 mutations is relatively severe, with a maculopathy in most patients and keratoconus and cataract in a large subset. Rod ERG abnormalities may be present in heterozygous carriers of AIPL1 mutations.

Clinical relevance: Understanding and recognizing the phenotype of LCA may help in defining the course and severity of the disease. Identifying the gene defect is the first step in preparation for therapy since molecular diagnosis in LCA will mandate the choice of treatment.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adolescent
  • Adult
  • Alleles
  • Blindness / congenital
  • Blindness / genetics*
  • Blindness / pathology
  • Carrier Proteins / genetics*
  • Cataract / congenital
  • Cataract / genetics
  • Cataract / pathology
  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • Electroretinography
  • Eye Proteins
  • Humans
  • Infant
  • Middle Aged
  • Mutation*
  • Phenotype*
  • Polymerase Chain Reaction
  • Polymorphism, Single-Stranded Conformational
  • Retinal Degeneration / congenital
  • Retinal Degeneration / genetics*
  • Retinal Degeneration / pathology
  • Visual Acuity


  • AIPL1 protein, human
  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • Eye Proteins