Japan Eye Genetics Consortium: National Cohort Survey and Whole Exome Sequencing Results of Cone-rod dystrophy

Abstract

Purpose : We describe the clinical and genetic characteristics of a nationwide cohort with cone-rod dystrophy (CORD) in the Japanese population.

Methods : A cohort of 205 affected and 96 unaffected subjects from 183 Japanese families diagnosed with CORD (i.e. progressive retinal dystrophy initially often affecting the macula with generalized cone dysfunction greater than rod dysfunction) or Stargardt disease was ascertained between 2008 and 2018. Families with occult macular dystrophy or achromatopsia were not included. The clinical diagnosis was performed with comprehensive ophthalmic examinations at 38 institutes throughout the nation. Whole exome sequencing with target analysis on 301 retinal diseases-associated genes, and in silico molecular genetic analysis was performed in 311 subjects from 183 families.

Results : There were 83 female and 122 male patients. The median age of onset of the probands was 31.0 years (range, 0-75), and the median age at the latest examination was 44.5 years (range, 7-84). The median visual acuity in the LogMAR unit was 0.52 (range, -0.08-2.00) in the right eye and 0.52 (-0.08-2.00) in the left eye. Disease-causing/associated variants were determined in 85/183 (46.4%) families, including 39 (39/85, 45.9%) families with previously reported variants and 46 families (46/85, 54.1%) families with novel variants. In total, 104 disease-causing/associated in the 17 genes were identified; ABCA4, CRX, GUCY2D, EYS, POC1B, PROM1, PRPH2, RPGR, KCNV2, PDE6C, and others.

Conclusions : Conclusive molecular genetic diagnosis was obtained in around half of this Japanese CORD cohort. Novel disease-causing/associated variants are frequently revealed, which suggests the distinctive genetic background of the Japanese population. This national survey provides epidemiologic evidence of Japanese CORD, which promotes patients’ care and therapeutic trials in the Japanese population.

This is a 2020 ARVO Annual Meeting abstract.