Abstract
Purpose: :
RPE65 plays an essential role in vitamin A metabolism necessary for the synthesis of the visual pigment chromophore 11-cis retinal. Mutations in RPE65 cause the childhood blindness known as Leber congenital amaurosis (LCA). The purpose of this study is to analyze the RPE65 mutations and clinical features of a Chinese family with LCA.
Methods: :
Detailed ocular examinations including visual acuity, slit lamp, fundus, electroretinography (ERG), optical coherent topography (OCT) and visual field were performed for affected subjects. Peripheral blood was obtained from all patients and their family members for genomic DNA extraction. The 14 exons of RPE65 were amplified by polymerase chain reaction (PCR) and screened for mutation by direct DNA sequencing. A hundred normal controls were screened to verify suspected diseased related mutations.
Results: :
The best corrected visual acuity of the affected sisters were 20/200 and 40/200 respectively. Severely depressed ERG and peripheral and central visual defect were observed. OCT showed near normal retinal micro-structure with detectable but thinned photoreceptor/RPE layer. Compound heterozygous missense mutations Leu67Arg and Tyr368Cys were identified in patients and segregated with the family. These mutations were not detected among 100 controls.
Conclusions: :
Compound heterozygous missense mutations Leu67Arg and Tyr368Cys were related to relative mild LCA phenotype. The identification and characterization of patients with RPE65 mutations is important for future clinical trials of rational therapies for LCA. To the best of our knowledge this is the first report of RPE65 mutations related to Chinese LCA patients.
Keywords: gene screening • retinal degenerations: hereditary • mutations