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. 2022 Dec;43(12):2251-2264.
doi: 10.1002/humu.24492. Epub 2022 Nov 7.

Genetic characterization of 1210 Japanese pedigrees with inherited retinal diseases by whole-exome sequencing

Akiko Suga  1 , Kazutoshi Yoshitake  1   2 , Naoko Minematsu  1 , Kazushige Tsunoda  3 , Kaoru Fujinami  3 , Yozo Miyake  4 , Kazuki Kuniyoshi  5 , Takaaki Hayashi  6 , Kei Mizobuchi  6 , Shinji Ueno  7   8 , Hiroko Terasaki  9 , Taro Kominami  7 , Nobuhisa Nao-I  10 , Go Mawatari  10 , Atsushi Mizota  11 , Kei Shinoda  11   12 , Mineo Kondo  13 , Kumiko Kato  13 , Tetsuju Sekiryu  14 , Makoto Nakamura  15 , Sentaro Kusuhara  15 , Hiroyuki Yamamoto  16 , Shuji Yamamoto  16 , Kiyofumi Mochizuki  17 , Hiroyuki Kondo  18 , Itsuka Matsushita  18 , Shuhei Kameya  19 , Takeo Fukuchi  20 , Tetsuhisa Hatase  20 , Masayuki Horiguchi  21 , Yoshiaki Shimada  21 , Atsuhiro Tanikawa  21 , Shuichi Yamamoto  22 , Gen Miura  22 , Nana Ito  22 , Akira Murakami  23 , Takuro Fujimaki  23   24 , Yoshihiro Hotta  25 , Koji Tanaka  26 , Takeshi Iwata  1
Affiliations

Genetic characterization of 1210 Japanese pedigrees with inherited retinal diseases by whole-exome sequencing

Akiko Suga et al. Hum Mutat. 2022 Dec.

Abstract

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.

Keywords: EYS; Japanese population; RP1; inherited retinal disease; retinitis pigmentosa; whole exome sequencing.

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References

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