Clinical and genetic characteristics of 15 affected patients from 12 Japanese families with GUCY2D-associated retinal disorder

Xiao Liu, Kaoru Fujinami, Kazuki Kuniyoshi, Mineo Kondo, Shinji Ueno, Takaaki Hayashi, Kiyofumi Mochizuki, Shuhei Kameya, Lizhu Yang, Yu Fujinami-Yokokawa, Gavin Arno, Nikolas Pontikos, Hiroyuki Sakuramoto, Taro Kominami, Hiroko Terasaki, Satoshi Katagiri, Kei Mizobuchi, Natsuko Nakamura, Kazutoshi Yoshitake, Yozo MiyakeShiying Li, Toshihide Kurihara, Kazuo Tsubota, Takeshi Iwata, Kazushige Tsunoda, Japan Eye Genetics Consortium

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12 Citations (Scopus)


Purpose: To determine the clinical and genetic characteristics of patients with GUCY2D-associated retinal disorder (GUCY2D-RD). Methods: Fifteen patients from 12 families with inherited retinal disorder (IRD) and harboring GUCY2D variants were ascertained from 730 Japanese families with IRD. Comprehensive ophthalmological examinations, including visual acuity (VA) measure-ment, retinal imaging, and electrophysiological assessment were performed to classify patients into three phenotype subgroups; macular dystrophy (MD), cone-rod dystrophy (CORD), and Leber congenital amaurosis (LCA). In silico analysis was performed for the detected variants, and the molecularly confirmed inheritance pattern was determined (autosomal dominant/recessive [AD/AR]). Results: The median age of onset/examination was 22.0/38.0 years (ranges, 0-55 and 1-73) with a median VA of 0.80/0.70 LogMAR units (ranges, 0.00-1.52 and 0.10-1.52) in the right/left eye, respectively. Macular atrophy was identified in seven patients (46.7%), and two had diffuse fundus disturbance (13.3%), and six had an essentially normal fundus (40.0%). There were 11 patients with generalized cone-rod dysfunction (78.6%), two with entire functional loss (14.3%), and one with confined macular dysfunction (7.1%). There were nine families with ADCORD, one with ARCORD, one with ADMD, and one with ARLCA. Ten GUCY2D variants were identified, including four novel variants (p.Val56GlyfsTer262, p.Met246Ile, p.Arg761Trp, p.Glu874Lys). Conclusions: This large cohort study delineates the disease spectrum of GUCY2D-RD. Diverse clinical presentations with various severities of ADCORD and the early-onset severe phenotype of ARLCA are illustrated. A relatively lower prevalence of GUCY2D-RD for ADCORD and ARLCA in the Japanese population was revealed. Translational Relevance: The obtained data help to monitor and counsel patients, especially in East Asia, as well as to design future therapeutic approaches.

Original languageEnglish
Article number2
JournalTranslational Vision Science and Technology
Issue number6
Publication statusPublished - 2020 May


  • Autosomal dominant
  • Cone rod dystrophy
  • GUCY2D
  • Leber congenital amaurosis
  • Macular dystrophy

ASJC Scopus subject areas

  • Biomedical Engineering
  • Ophthalmology


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