TY - JOUR
T1 - Clinical and genetic characteristics of 10 Japanese patients with PROM1-associated retinal disorder
T2 - A report of the phenotype spectrum and a literature review in the Japanese population
AU - Fujinami, Kaoru
AU - Oishi, Akio
AU - Yang, Lizhu
AU - Arno, Gavin
AU - Pontikos, Nikolas
AU - Yoshitake, Kazutoshi
AU - Fujinami-Yokokawa, Yu
AU - Liu, Xiao
AU - Hayashi, Takaaki
AU - Katagiri, Satoshi
AU - Mizobuchi, Kei
AU - Mizota, Atsushi
AU - Shinoda, Kei
AU - Nakamura, Natsuko
AU - Kurihara, Toshihide
AU - Tsubota, Kazuo
AU - Miyake, Yozo
AU - Iwata, Takeshi
AU - Tsujikawa, Akitaka
AU - Tsunoda, Kazushige
N1 - Funding Information:
Kaoru Fujinami is supported by grants from Grant-in-Aid for Young Scientists (A) of the Ministry of Education, Culture, Sports, Science and Technology, Japan (16H06269), grants from Grant-in-Aid for Scientists to support international collaborative studies of the Ministry of Education, Culture, Sports, Science and Technology, Japan (16KK01930002), grants from National Hospital Organization Network Research Fund (H30-NHO-Sensory Organs-03), grants from FOUNDATION FIGHTING BLINDNESS ALAN LATIES CAREER DEVELOPMENT PROGRAM (CF-CL-0416-0696-UCL), grants from Health Labour Sciences Research Grant, The Ministry of Health Labour and Welfare (201711107A), and grants from Great Britain Sasakawa Foundation Butterfield Awards. Akio Oishi is supported by grants from, Japan Society for the Promotion of Science, Tokyo, Japan (17H06820 and 19K09929). Yu Fujinami-Yokokawa is supported by grants from Grant-in-Aid for Young Scientists of the Ministry of Education, Culture, Sports, Science and Technology, Japan (18K16943). Gavin Arno is supported by a Fight for Sight (UK) Early career investigator award, NIHR-BRC at Moorfields Eye Hospital and the UCL Institute of Ophthalmology, NIHR-BRC at Great Ormond Street Hospital and UCL Institute of Child Health, and Great Britain Sasakawa Foundation Butterfield Award, UK. Nikolas Pontikos is funded by a Moorfields Eye Charity Career Development Award (R190031A), the NIHR-BRC at Moorfields Eye Hospital and the UCL Institute of Ophthalmology. Toshihide Kurihara is supported by Tsubota Laboratory, Inc, Fuji Xerox Co., Ltd, Kirin Company, Ltd, Kowa Company, Ltd, Novartis Pharmaceuticals Japan, Santen Pharmaceutical Co. Ltd, and ROHTO Pharmaceutical Co., Ltd. Takeshi Iwata is supported by Japan Agency for Medical Research and Development (AMED) (18ek0109282h0002). Kazushige Tsunoda is supported by AMED, the Ministry of Health, Labor and Welfare, Japan (18ek0109282h0002), Grants-in-Aid for Scientific Research, Japan Society for the Promotion of Science, Japan (H26-26462674), grants from National Hospital Organization Network Research Fund, Japan (H30-NHO-Sensory Organs-03) and Novartis Research Grant (2018).
PY - 2020/9/1
Y1 - 2020/9/1
N2 - 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.
AB - 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.
KW - PROM1
KW - autosomal dominant
KW - cone dystrophy
KW - cone rod dystrophy
KW - macular dystrophy
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U2 - 10.1002/ajmg.c.31826
DO - 10.1002/ajmg.c.31826
M3 - Article
C2 - 32820593
AN - SCOPUS:85089579826
VL - 184
SP - 656
EP - 674
JO - American Journal of Medical Genetics, Part C: Seminars in Medical Genetics
JF - American Journal of Medical Genetics, Part C: Seminars in Medical Genetics
SN - 1552-4868
IS - 3
ER -