RPE65 Mutations in Two Japanese Families with Leber Congenital Amaurosis

To investigate genetic and clinical features of patients with Leber congenital amaurosis (LCA) caused by RPE65 mutations.

Five Japanese families with LCA were recruited. We performed complete ophthalmic examinations, with optical coherence tomography, fundus autofluorescence imaging, and full-field electroretinography (ERG). Genetic analysis was performed with whole-exome sequencing analysis and Sanger sequencing.

We identified RPE65 mutations in two unrelated LCA patients from two families. Case 1: A 5-month-old girl was diagnosed with LCA because of nystagmus, loss of vision and non-recordable ERG. She was the only one affected in her non-consanguineous family, and exhibited novel compound heterozygous RPE65 mutations (c.177C>G, p.H59Q and c.183_184insT, p.D62X). Case 2: A 30-year-old woman, who had night blindness and poor ocular pursuit during the first year of life, exhibited severe retinal degeneration and non-recordable ERG. She was the only affected in her non-consanguineous family, and showed a homozygous RPE65 mutation (c.1543C>T, p.R515W).

By using whole-exome sequencing analysis, three RPE65 mutations were identified in two Japanese patients with LCA. This approach would be useful for identification of disease-causing mutations of LCA.