Genetic Etiology and Clinical Features of Achromatopsia in Japan

Abstract

Purpose: To ascertain the characteristics of achromatopsia (ACHM) in Japan by analyzing the genetic and phenotypic features of patients with ACHM. Methods: The medical records of 52 patients from 47 Japanese families who were clinically diagnosed with ACHM were reviewed in this retrospective observational study. Results: Thirty-six causative variants of ACHM were identified in 26 families via whole-exome sequencing (WES): PDE6C (12 families), CNGA3 (10 families), CNGB3 (two families), and GNAT2 (two families). However, none of the six causative variants that are known to cause ACHM, or the 281 other genes listed in RetNet, were observed in 19 families. A significant trend toward older age and worsening of ellipsoid zone disruption on optical coherence tomography images was observed (P < 0.01). Progressive ellipsoid zone disruptions were observed in 13 eyes of seven patients during the follow-up visits. These patients harbored one or more variants in PDE6C. Conclusions: The ACHM phenotype observed in this study was similar to those observed in previous reports; however, the causative gene variants differed from those in Europe. The low identification ratio of causative genes in WES suggests the presence of unique hot spots in Japanese patients with ACHM that were not detectable via ordinal WES.