The phenotype of Leber congenital amaurosis in patients with AIPL1 mutations

Sharola Dharmaraj, Bart P. Leroy, Melanie M. Sohocki, Robert K. Koenekoop, Isabelle Perrault, Khalid Anwar, Shagufta Khaliq, R. Summathi Devi, David G. Birch, Elaine De Pool, Natalio Izquierdo, Lionel Van Maldergem, Mohammad Ismail, Annette M. Payne, Graham E. Holder, Shomi S. Bhattacharya, Alan C. Bird, Josseline Kaplan, Irene H. Maumenee

Research output: Contribution to journalArticlepeer-review

78 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1029-1037
Number of pages9
JournalArchives of ophthalmology
Issue number7
StatePublished - Jul 2004

ASJC Scopus subject areas

  • Ophthalmology


Dive into the research topics of 'The phenotype of Leber congenital amaurosis in patients with AIPL1 mutations'. Together they form a unique fingerprint.

Cite this