Phenotypic expansion of autosomal dominant retinitis pigmentosa associated with the D477G mutation in RPE65

• DOI: 10.1101/mcs.a004952
• Publication Date: 2020-02-03T19:45:18Z
• Authors: Ruben Jauregui; Ahra Cho; Jin Kyun Oh; Akemi J. Tanaka; Janet R. Sparrow; Stephen H. Tsang
• Keywords: Research Report; Male; cis-trans-Isomerases; Genotype; Retinal Pigment Epithelium; Middle Aged; 03 medical and health sciences; Phenotype; 0302 clinical medicine; Amino Acid Substitution; Mutation; Humans; Alleles; Genetic Association Studies; Retinitis Pigmentosa; Genes, Dominant

Mutations in the gene RPE65 (OMIM: 180069) are recessively inherited and known to cause Leber congenital amaurosis. Recently, the mutation D477G in RPE65 has been identified as a cause of autosomal dominant retinitis pigmentosa (RP). Variable expressivity of this disease has been reported, as carrier individuals can present with mild, nonpenetrant, or, most commonly, a severe chorioretinal phenotype that resembles choroideremia. We report the case of a 57-yr-old male who presented to our clinic with nyctalopia and decreasing visual acuity for 1 yr. Dilated fundus examination revealed retinal atrophy and peripheral mottling of the retinal pigment epithelium (RPE). SW-AF revealed patchy hypoautofluorescence throughout the posterior pole with separate lacunae-like areas in the macula of severe RPE atrophy along with foveal sparing. Full-field electroretinogram suggested a rod–cone dystrophy. Whole-exome sequencing revealed the heterozygous mutation c.1430A > G (p.D477G) in the RPE65 gene. This phenotype of peripheral RPE mottling and severe macular lacunae-like atrophy has not been previously reported with RPE65 autosomal dominant RP, supporting the variable expressivity of the disease and expanding the known phenotypic presentations.