The Phenotype of Leber Congenital Amaurosis in Patients With AIPL1 Mutations

OBJECTIVES To describe the phenotype of Leber congenital amaurosis (LCA) in 26probands with mutations in aryl hydrocarbon receptor interacting protein-like1 protein (AIPL1) and compare it with phenotypesof other LCA-related genes. To describe the electroretinogram (ERG) in heterozygotecarriers. METHODS Patients with AIPL1-related LCA were identifiedin a cohort of 303 patients with LCA by polymerase chain reaction single-strandconfirmational polymorphism mutation screening and/or direct sequencing. Phenotypiccharacterization included clinical and ERG evaluation. Seven heterozygouscarrier 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 rangedfrom light perception to 20/400. Variable retinal appearances, ranging fromnear normal to varying degrees of chorioretinal atrophy and intraretinal pigmentmigration, were noted. Atrophic and/or pigmentary macular changes were presentin 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 heterozygotecarrier revealed significantly reduced rod function, while ERGs for 6 othercarrier parents were normal. CONCLUSIONS The phenotype of LCA in patients with AIPL1 mutationsis relatively severe, with a maculopathy in most patients and keratoconusand cataract in a large subset. Rod ERG abnormalities may be present in heterozygouscarriers of AIPL1 mutations. CLINICAL RELEVANCE Understanding and recognizing the phenotype of LCA may help in definingthe course and severity of the disease. Identifying the gene defect is thefirst step in preparation for therapy since molecular diagnosis in LCA willmandate the choice of treatment.Arch Ophthalmol. 2004;122:1029-1037-->