Clinical and genetic characteristics of 14 patients from 13 Japanese families with RPGR-associated retinal disorder: report of eight novel variants

Go Mawatari; Kaoru Fujinami; Xiao Liu; Lizhu Yang; Yu-Fujinami Yokokawa; Shiori Komori; Shinji Ueno; Hiroko Terasaki; Satoshi Katagiri; Takaaki Hayashi; Kazuki Kuniyoshi; Yozo Miyake; Kazushige Tsunoda; Kazutoshi Yoshitake; Takeshi Iwata; Nobuhisa Nao-I; JEGC study group

doi:10.1038/s41439-019-0065-7

Clinical and genetic characteristics of 14 patients from 13 Japanese families with RPGR-associated retinal disorder: report of eight novel variants

Hum Genome Var. 2019 Aug 2:6:34. doi: 10.1038/s41439-019-0065-7. eCollection 2019.

Authors

Go Mawatari¹, Kaoru Fujinami^{2

3

4

5}, Xiao Liu^{2

3

6}, Lizhu Yang^{2

3}, Yu-Fujinami Yokokawa^{2

7

8}, Shiori Komori⁹, Shinji Ueno⁹, Hiroko Terasaki⁹, Satoshi Katagiri¹⁰, Takaaki Hayashi¹⁰, Kazuki Kuniyoshi¹¹, Yozo Miyake^{2

12}, Kazushige Tsunoda², Kazutoshi Yoshitake¹³, Takeshi Iwata¹³, Nobuhisa Nao-I¹; JEGC study group

Affiliations

¹ 1Department of Ophthalmology, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki, Japan.
² 2Laboratory of Visual Physiology, Division of Vision Research, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Meguro-ku, Tokyo, Japan.
³ 3Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan.
⁴ 4UCL Institute of Ophthalmology, London, UK.
⁵ 5Moorfields Eye Hospital, London, UK.
⁶ 6Southwest Hospital/Southwest Eye Hospital, Third Military Medical University, Chongqing, China.
⁷ 7Graduate School of Health Management, Keio University, Tokyo, Japan.
⁸ Division of Public Health, Yokokawa Clinic, Suita, Osaka, Japan.
⁹ 9Department of Ophthalmology, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Aichi Japan.
¹⁰ 10Department of Ophthalmology, The Jikei University School of Medicine, Nishi-Shimbashi, Minato-ku, Tokyo, Japan.
¹¹ 11Department of Ophthalmology, Kinki University Faculty of Medicine, Osaka-Sayama City, Osaka, Japan.
¹² Kobe Eye Center, Next Vision, Kobe, Hyogo, Japan.
¹³ 13Division of Molecular and Cellular Biology, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Meguro-ku, Tokyo, Japan.

Abstract

Variants in the retinitis pigmentosa GTPase regulator (RPGR) gene are a major cause of X-linked inherited retinal disorder (IRD). We herein describe the clinical and genetic features of 14 patients from 13 Japanese families harboring RPGR variants in a nationwide cohort. Comprehensive ophthalmological examinations were performed to classify the patients into one of the phenotype subgroups: retinitis pigmentosa (RP) and cone rod dystrophy (CORD). The mean age of onset/at examination was 13.8/38.1 years (range, 0-50/11-72), respectively. The mean visual acuity in the right/left eye was 0.43/0.43 (range, 0.1-1.7/-0.08-1.52) LogMAR unit. Eight patients had RP, and six had CORD. Whole-exome sequencing with target analyses identified 13 RPGR variants in 730 families with IRD, including 8 novel variants. An association between the phenotype subgroup and the position of variants (cutoff of amino acid 950) was revealed. To conclude, the clinical and genetic spectrum of RPGR-associated retinal disorder was first illustrated in a Japanese population, with a high proportion of novel variants. These results suggest the distinct genetic background of RPGR in the Japanese population, in which the genotype-phenotype association was affirmed. This evidence should be helpful monitoring and counseling patients and in selecting patients for future therapeutic trials.

Keywords: Genetic predisposition to disease; Medical genetics.