Genetics in Medicine Open (Jan 2024)
A homozygous structural variant of RPGRIP1 is frequently associated with achromatopsia in Japanese patients with IRD
- Akiko Suga,
- Kei Mizobuchi,
- Taiga Inooka,
- Kazutoshi Yoshitake,
- Naoko Minematsu,
- Kazushige Tsunoda,
- Kazuki Kuniyoshi,
- Yosuke Kawai,
- Yosuke Omae,
- Katsushi Tokunaga,
- Takaaki Hayashi,
- Shinji Ueno,
- Takeshi Iwata,
- Hatsue Ishibashi-Ueda,
- Tsutomu Tomita,
- Michio Noguchi,
- Ayako Takahashi,
- Yu-ichi Goto,
- Sumiko Yoshida,
- Kotaro Hattori,
- Ryo Matsumura,
- Aritoshi Iida,
- Yutaka Maruoka,
- Hiroyuki Gatanaga,
- Masaya Sugiyama,
- Satoshi Suzuki,
- Kengo Miyo,
- Yoichi Matsubara,
- Akihiro Umezawa,
- Kenichiro Hata,
- Tadashi Kaname,
- Kouichi Ozaki,
- Haruhiko Tokuda,
- Hiroshi Watanabe,
- Shumpei Niida,
- Eisei Noiri,
- Koji Kitajima,
- Yosuke Omae,
- Reiko Miyahara,
- Hideyuki Shimanuki,
- Yosuke Kawai,
- Katsushi Tokunaga
Affiliations
- Akiko Suga
- Division of Molecular and Cellular Biology, National Institute of Sensory Organs, NHO Tokyo Medical Center, Tokyo, Japan
- Kei Mizobuchi
- Department of Ophthalmology, The Jikei University School of Medicine, Tokyo, Japan
- Taiga Inooka
- Department of Ophthalmology, Nagoya University Graduate School of Medicine, Aichi, Japan
- Kazutoshi Yoshitake
- Laboratory of Aquatic Molecular Biology and Biotechnology, Aquatic Bioscience, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan
- Naoko Minematsu
- Division of Molecular and Cellular Biology, National Institute of Sensory Organs, NHO Tokyo Medical Center, Tokyo, Japan
- Kazushige Tsunoda
- Division of Vision Research, National Institute of Sensory Organs, NHO Tokyo Medical Center, Tokyo, Japan
- Kazuki Kuniyoshi
- Department of Ophthalmology, Kindai University Faculty of Medicine, Osaka, Japan
- Yosuke Kawai
- Genome Medical Science Project, National Center for Global Health and Medicine, Tokyo, Japan
- Yosuke Omae
- Genome Medical Science Project, National Center for Global Health and Medicine, Tokyo, Japan
- Katsushi Tokunaga
- Genome Medical Science Project, National Center for Global Health and Medicine, Tokyo, Japan
- Takaaki Hayashi
- Department of Ophthalmology, The Jikei University School of Medicine, Tokyo, Japan; Takaaki Hayashi, Department of Ophthalmology, The Jikei University School of Medicine, 3-25-8 Nishi-shimbashi, Minato-ku, Tokyo 105-8461, Japan.
- Shinji Ueno
- Department of Ophthalmology, Hirosaki University Graduate School of Medicine, Aomori, Japan; Shinji Ueno, Department of Ophthalmology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho Hirosaki-shi, Aomori 036-8562, Japan.
- Takeshi Iwata
- Division of Molecular and Cellular Biology, National Institute of Sensory Organs, NHO Tokyo Medical Center, Tokyo, Japan; Correspondence and requests for materials should be addressed to Takeshi Iwata, Division of Molecular and Cellular Biology, National Institute of Sensory Organs, NHO Tokyo Medical Center, 2-5-1, Higashigaoka Meguro-ku, Tokyo 152-8902 Japan.
- Hatsue Ishibashi-Ueda
- Tsutomu Tomita
- Michio Noguchi
- Ayako Takahashi
- Yu-ichi Goto
- Sumiko Yoshida
- Kotaro Hattori
- Ryo Matsumura
- Aritoshi Iida
- Yutaka Maruoka
- Hiroyuki Gatanaga
- Masaya Sugiyama
- Satoshi Suzuki
- Kengo Miyo
- Yoichi Matsubara
- Akihiro Umezawa
- Kenichiro Hata
- Tadashi Kaname
- Kouichi Ozaki
- Haruhiko Tokuda
- Hiroshi Watanabe
- Shumpei Niida
- Eisei Noiri
- Koji Kitajima
- Yosuke Omae
- Reiko Miyahara
- Hideyuki Shimanuki
- Yosuke Kawai
- Katsushi Tokunaga
- Journal volume & issue
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Vol. 2
p. 101843
Abstract
Purpose: Achromatopsia (ACHM) is an early-onset cone dysfunction caused by 5 genes with cone-specific functions (CNGA3, CNGB3, GNAT2, PDE6C, and PDE6H) and by ATF6, a transcription factor with ubiquitous expression. To improve the relatively low variant detection ratio in these genes in a cohort of exome-sequenced Japanese patients with inherited retinal diseases (IRD), we performed genome sequencing to detect structural variants and intronic variants in patients with ACHM. Methods: Genome sequencing of 10 ACHM pedigrees was performed after exome sequencing. Structural, non-coding, and coding variants were filtered based on segregation between the affected and unaffected in each pedigree. Variant frequency and predicted damage scores were considered in identifying pathogenic variants. Results: A homozygous deletion involving exon 18 of RPGRIP1 was detected in 5 of 10 ACHM probands, and variant inheritance from each parent was confirmed. This deletion was relatively frequent (minor allele frequency = 0.0023) in the Japanese population but was only homozygous in patients with ACHM among the 199 Japanese IRD probands analyzed by the same genome sequencing pipeline. Conclusion: The deletion involving exon 18 of RPGRIP1 is a prevalent cause of ACHM in Japanese patients and contributes to the wide spectrum of RPGRIP1-associated IRD phenotypes, from Leber congenital amaurosis to ACHM.
