Prevalence of AIPL1 mutations in inherited retinal degenerative disease

Leber congenital amaurosis (LCA) is the most severe form of inherited retin al dystrophy and the most frequent cause of inherited blindness in children . LCA is usually inherited in an autosomal recessive fashion, although rare dominant cases have been reported. One form of LCA, LCA4, maps to chromoso me 17p13 and is genetically distinct from other forms of LCA, We recently i dentified the gene associated with LCA4, AIPL1 (aryl-hydrocarbon interactin g protein-like 1) and identified three mutations that were the cause of bli ndness in five families with LCA, In this study, AIPL1 was screened for mut ations in 512 unrelated probands with a range of retinal degenerative disea ses to determine if AIPL1 mutations cause other forms of inherited retinal degeneration and to determine the relative contribution of AIPL1 mutations to inherited retinal disorders in populations worldwide. We identified 11 L CA families whose retinal disorder is caused by homozygous or compound hete rozygous AIPL1 mutations. We also identified affected individuals in two ap parently dominant families, diagnosed with juvenile retinitis pigmentosa or dominant cone-rod dystrophy, respectively, who are heterozygous for a 12-b p AIPL1 deletion. Our results suggest that AIPL1 mutations cause approximat ely 7% of LCA worldwide and may cause dominant retinopathy, (C) 2000 Academ ic Press.