Suga Akiko, Yoshitake Kazutoshi, Minematsu Naoko, Tsunoda Kazushige, Fujinami Kaoru, Miyake Yozo, Kuniyoshi Kazuki, Hayashi Takaaki, Mizobuchi Kei, Ueno Shinji, Terasaki Hiroko, Kominami Taro, Nao-I Nobuhisa, Mawatari Go, Mizota Atsushi, Shinoda Kei, Kondo Mineo, Kato Kumiko, Sekiryu Tetsuju, Nakamura Makoto, Kusuhara Sentaro, Yamamoto Hiroyuki, Yamamoto Shuji, Mochizuki Kiyofumi, Kondo Hiroyuki, Matsushita Itsuka, Kameya Shuhei, Fukuchi Takeo, Hatase Tetsuhisa, Horiguchi Masayuki, Shimada Yoshiaki, Tanikawa Atsuhiro, Yamamoto Shuichi, Miura Gen, Ito Nana, Murakami Akira, Fujimaki Takuro, Hotta Yoshihiro, Tanaka Koji, Iwata Takeshi
Division of Molecular and Cellular Biology, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan.
Laboratory of Aquatic Molecular Biology and Biotechnology, Aquatic Bioscience, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.
Hum Mutat. 2022 Dec;43(12):2251-2264. doi: 10.1002/humu.24492. Epub 2022 Nov 7.
Inherited retinal diseases (IRDs) comprise a phenotypically and genetically heterogeneous group of ocular disorders that cause visual loss via progressive retinal degeneration. Here, we report the genetic characterization of 1210 IRD pedigrees enrolled through the Japan Eye Genetic Consortium and analyzed by whole exome sequencing. The most common phenotype was retinitis pigmentosa (RP, 43%), followed by macular dystrophy/cone- or cone-rod dystrophy (MD/CORD, 13%). In total, 67 causal genes were identified in 37% (448/1210) of the pedigrees. The first and second most frequently mutated genes were EYS and RP1, associated primarily with autosomal recessive (ar) RP, and RP and arMD/CORD, respectively. Examinations of variant frequency in total and by phenotype showed high accountability of a frequent EYS missense variant (c.2528G>A). In addition to the two known EYS founder mutations (c.4957dupA and c.8805C>G) of arRP, we observed a frequent RP1 variant (c.5797C>T) in patients with arMD/CORD.
遗传性视网膜疾病（IRDs）是一组表型和基因均具有异质性的眼部疾病，通过进行性视网膜变性导致视力丧失。在此，我们报告了通过日本眼遗传联盟招募并经全外显子组测序分析的1210个IRD家系的基因特征。最常见的表型是色素性视网膜炎（RP，43%），其次是黄斑营养不良/视锥或视锥 - 视杆营养不良（MD/CORD，13%）。总共在37%（448/1210）的家系中鉴定出67个致病基因。最常发生突变的第一个和第二个基因分别是EYS和RP1，主要分别与常染色体隐性（ar）RP以及RP和arMD/CORD相关。对总体及按表型分类的变异频率进行检查显示，一个常见的EYS错义变异（c.2528G>A）具有较高的致病可能性。除了arRP的两个已知EYS始祖突变（c.4957dupA和c.8805C>G）外，我们在arMD/CORD患者中观察到一个常见的RP1变异（c.5797C>T）。
