Clinical and genetic characteristics of 10 Japanese patients with <scp><i>PROM1</i></scp>‐associated retinal disorder: A report of the phenotype spectrum and a literature review in the Japanese population
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
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.