A new PDE6A missense variant p.Arg544Gln in rod–cone dystrophy

Thus far, only one Japanese patient with autosomal recessive rod–cone dystrophy (AR-RCD) associated with the phosphodiesterase 6A gene (PDE6A) has been reported. The purpose of this study was to analyze the clinical features of a Japanese female patient with AR-RCD with a novel missense variant in PDE6A. We performed whole-exome sequencing (WES) to identify the disease-causing variant and a comprehensive ophthalmic examination including full-field electroretinography (ERG). WES analysis revealed that the patient carried a novel homozygous missense variant (c.1631G > A; p.Arg544Gln) in PDE6A. Her unaffected parents carried the heterozygous variant. The patient reported night blindness in her early 20 s. At the age of 25 years, she underwent a comprehensive ophthalmic examination. Her corrected visual acuity was 20/13 in the right and 20/10 in the left eyes. Fundus images showed degenerative changes with bone spicule pigmentation in the mid-peripheral retina, and peripheral retinal vessels were not attenuated. Ultra-wide-field fundus autofluorescence images demonstrated large hypoautofluorescent regions corresponding to the degenerative changes, surrounded by hyperautofluorescence. Cross-sectional optical coherence tomography demonstrated a preserved ellipsoid zone and retinal thickness in the center of the macula, with perifoveal atrophy. ERG responses were subnormal, revealing that rod-mediated responses were more affected than cone-mediated responses, consistent with findings observed in RCD. This is the second case of a patient with AR-RCD associated with PDE6A in the Japanese population. These findings will contribute to a better clinical understanding of PDE6A-associated RCD and valuable insights for gene therapy trials.