Natsuki Higa ¹ Takaaki Hayashi ^1* Kei Mizobuchi ¹ Maki Iwasa ² Shingo Kubota ³ Kazuki Kuniyoshi ⁴ Shuhei Kameya ⁵ HIROYUKI KONDO ⁶ Mineo Kondo ⁷ Tadashi Nakano ¹

• ¹ Department of Ophthalmology, Jikei Medical University School of Medicine, Tokyo, Japan
• ² Shiga University of Medical Science, Otsu, Shiga, Japan
• ³ Kubota Eye Clinic, Utsunomiya, Japan
• ⁴ Department of Ophthalmology, Faculty of Medicine, Kindai University, Higashi-osaka, Ōsaka, Japan
• ⁵ Kameya Eye Clinic, Inzai, Japan
• ⁶ Department of Ophthalmology, University of Occupational and Environmental Health, Fukuoka, Japan
• ⁷ Department of Ophthalmology, Mie University Hospital, Tsu City, Japan

In Japan, inherited retinal dystrophy caused by biallelic variants of the RPE65 gene is exceedingly rare. The purpose of this study was to describe a Japanese male patient with a novel variant in RPE65 associated with Leber congenital amaurosis (LCA). Case report: The patient, diagnosed with LCA, exhibited infantile nystagmus and reported experiencing night blindness since early childhood. At 27 years of age, the patient underwent an ophthalmologically evaluation. Corrected visual acuity was Snellen equivalent 20/133 in the right eye and Snellen equivalent 20/100 in the left eye. Fundus examination revealed alterations in the retinal pigment epithelium characterized by hypopigmentation and narrowing of retinal vessels. Fundus autofluorescence imaging demonstrated a generally diminished autofluorescent signal. Full-field electroretinography identified a generalized dysfunction of both rod and cone systems in each eye. Whole exome sequencing identified a novel missense variant in RPE65 (NM_000329.3): c.1172C>A p.(Ala391Asp), which was classified as pathogenic, as well as a recurrent variant p.(Arg515Trp).This study provides valuable insights into the genotype-phenotype correlation of RPE65-associated LCA in Japanese patients, with critical implications for enhanced diagnostic accuracy and informed therapeutic decisions.