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Clinical and genetic characteristics of 10 Japanese patients with PROM1‐associated retinal disorder: A report of the phenotype spectrum and a literature review in the Japanese population |
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| Authors: | Kaoru Fujinami Akio Oishi Lizhu Yang Gavin Arno Nikolas Pontikos Kazutoshi Yoshitake Yu Fujinami‐Yokokawa Xiao Liu Takaaki Hayashi Satoshi Katagiri Kei Mizobuchi Atsushi Mizota Kei Shinoda Natsuko Nakamura Toshihide Kurihara Kazuo Tsubota Yozo Miyake Takeshi Iwata Akitaka Tsujikawa Kazushige Tsunoda Japan Eye Genetics Consortium study group |
| Affiliation: | 1. https://orcid.org/0000-0003-4248-0033;2. Laboratory of Visual Physiology, Division of Vision Research, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan;3. Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan;4. UCL Institute of Ophthalmology, London, UK;5. Moorfields Eye Hospital, London, UK;6. Kaoru Fujinami, 2‐5‐1, Higashigaoka, Meguro‐ku, Laboratory of Visual Physiology, Division for Vision Research, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, 152‐8902 Japan.;7. Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan;8. North East Thames Regional Genetics Service, UCL Great Ormond Street Institute of Child Health, Great Ormond Street NHS Foundation Trust, London, UK;9. Division of Molecular and Cellular Biology, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan;10. Department of Health Policy and Management, Keio University School of Medicine, Tokyo, Japan;11. Division of Public Health, Yokokawa Clinic, Suita, Japan;12. Southwest Hospital/Southwest Eye Hospital, Third Military Medical University (Army Medical University), Chongqing, China;13. Department of Ophthalmology, The Jikei University School of Medicine, Tokyo, Japan;14. Department of Ophthalmology, Teikyo University, Tokyo, Japan;15. Department of Ophthalmology, Saitama Medical University, Saitama, Japan;16. Department of Ophthalmology, The University of Tokyo, Tokyo, Japan;17. Aichi Medical University, Nagakute, Japan;18. Next vision, Kobe Eye Center, Hyogo, Japan;19. The JEGC Study Group members are as follows: Chair's Office: National Institute of Sensory Organs, Takeshi Iwata, Kazushige Tsunoda, Kaoru Fujinami, Shinji Ueno, Kazuki Kuniyoshi, Takaaki Hayashi, Mineo Kondo, Atsushi Mizota, Nobuhisa Naoi, Kei Shinoda, Shuhei Kameya, Hiroyuki Kondo, Taro Kominami, Hiroko Terasaki, Hiroyuki Sakuramoto, Satoshi Katagiri, Kei Mizobuchi, Natsuko Nakamura, Go Mawatari, Toshihide Kurihara, Kazuo Tsubota, Yozo Miyake, Kazutoshi Yoshitake, Toshihide Nishimura, Yoshihide Hayashizaki, Nobuhiro Shimozawa, Masayuki Horiguchi, Shuichi Yamamoto, Manami Kuze, Shigeki Machida, Yoshiaki Shimada, Makoto Nakamura, Takashi Fujikado, Yoshihiro Hotta, Masayo Takahashi, Kiyofumi Mochizuki, Akira Murakami, Hiroyuki Kondo, Susumu Ishida, Mitsuru Nakazawa, Tetsuhisa Hatase, Tatsuo Matsunaga, Akiko Maeda, Kosuke Noda, Atsuhiro Tanikawa, Syuji Yamamoto, Hiroyuki Yamamoto, Makoto Araie, Makoto Aihara, Toru Nakazawa, Tetsuju Sekiryu, Kenji Kashiwagi, Kenjiro Kosaki, Carninci Piero, Takeo Fukuchi, Atsushi Hayashi, Katsuhiro Hosono, Keisuke Mori, Kouji Tanaka, Koichi Furuya, Keiichirou Suzuki, Ryo Kohata, Yasuo Yanagi, Yuriko Minegishi, Daisuke Iejima, Akiko Suga, Brian P. Rossmiller, Yang Pan, Tomoko Oshima, Mao Nakayama, Megumi Yamamoto, Naoko Minematsu, Daisuke Mori, Yusuke Kijima, Kentaro Kurata, Norihiro Yamada, Masayoshi Itoh, Hideya Kawaji, Yasuhiro Murakawa, Ryo Ando, Wataru Saito, Yusuke Murakami, Hiroaki Miyata, Lizhu Yang, Yu Fujinami‐Yokokawa, Xiao Liu, Gavin Arno, Nikolas Pontikos, Kazuki Yamazawa, Satomi Inoue, Takayuki Kinoshita. |
| Abstract: | Variants in the PROM1 gene are associated with cone (?rod) dystrophy, macular dystrophy, and other phenotypes. We describe the clinical and genetic characteristics of 10 patients from eight Japanese families with PROM1‐associated retinal disorder (PROM1‐RD) in a nationwide cohort. A literature review of PROM1‐RD in the Japanese population was also performed. The median age at onset/examination of 10 patients was 31.0 (range, 10–45)/44.5 (22–73) years. All 10 patients showed atrophic macular changes. Seven patients (70.0%) had spared fovea to various degrees, approximately half of whom had maintained visual acuity. Generalized cone (?rod) dysfunction was demonstrated in all nine subjects with available electrophysiological data. Three PROM1 variants were identified in this study: one recurrent disease‐causing variant (p.Arg373Cys), one novel putative disease‐causing variant (p.Cys112Arg), and one novel variant of uncertain significance (VUS; p.Gly53Asp). Characteristic features of macular atrophy with generalized cone‐dominated retinal dysfunction were shared among all 10 subjects with PROM1‐RD, and the presence of foveal sparing was crucial in maintaining visual acuity. Together with the three previously reported variants [p.R373C, c.1551+1G>A (pathogenic), p.Asn580His (likely benign)] in the literature of Japanese patients, one prevalent missense variant (p.Arg373Cys, 6/9 families, 66.7%) detected in multiple studies was determined in the Japanese population, which was also frequently detected in the European population. |
| Keywords: | autosomal dominant cone dystrophy cone rod dystrophy macular dystrophy PROM1 |