Retinal dehydrogenase 12 (RDH12) mutations in leber congenital amaurosis

Abstract

Leber congenital amaurosis (LCA), the most early-onset and severe form of all inherited retinal dystrophies, is responsible for congenital blindness. Ten LCA genes have been mapped, and seven of these have been identified. Because some of these genes are involved in the visual cycle, we regarded the retinal pigment epithelium and photoreceptor-specific retinal dehydrogenase (RDH) genes as candidate genes in LCA. Studying a series of 110 unrelated patients with LCA, we found mutations in the photoreceptor-specific RDH12 gene in a significant subset of patients (4.1%). Interestingly, all patients harboring RDH12 mutations had a severe yet progressive rod-cone dystrophy with severe macular atrophy but no or mild hyperopia.

Figure 1

Pedigrees and segregation analysis of RDH12 disease-causing mutations in eight families with LCA

Figure 2

Amino acid sequences of human and mouse RDH12 and of human RDH8, RDH10, RDH11, RDH13, and RDH14, deduced from cDNA sequences (GenBank accession numbers BC025724, BC016204, NM_015725, BC067131, BC011727, BC009881, and BC009830, respectively) and conservation of amino acids mutated in patients with LCA.