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author Tsuboi, Takeru
Mizobuchi, Kei
Yoshitake, Kazutoshi
Kuniyoshi, Kazuki
Kominami, Taro
Ueno, Shinji
Nishiguchi, Koji M
Kusaka, Shunji
Iwata, Takeshi
Hayashi, Takaaki
Nakano, Tadashi
author_facet Tsuboi, Takeru
Mizobuchi, Kei
Yoshitake, Kazutoshi
Kuniyoshi, Kazuki
Kominami, Taro
Ueno, Shinji
Nishiguchi, Koji M
Kusaka, Shunji
Iwata, Takeshi
Hayashi, Takaaki
Nakano, Tadashi
Tsuboi, Takeru
Mizobuchi, Kei
Yoshitake, Kazutoshi
Kuniyoshi, Kazuki
Kominami, Taro
Ueno, Shinji
Nishiguchi, Koji M
Kusaka, Shunji
Iwata, Takeshi
Hayashi, Takaaki
Nakano, Tadashi
collection PubMed - marine biology
contents Clinical and genetic characterization of REEP6-associated retinopathy in a Japanese cohort. Tsuboi, Takeru Mizobuchi, Kei Yoshitake, Kazutoshi Kuniyoshi, Kazuki Kominami, Taro Ueno, Shinji Nishiguchi, Koji M Kusaka, Shunji Iwata, Takeshi Hayashi, Takaaki Nakano, Tadashi Humans Female Male Retrospective Studies Japan Tomography, Optical Coherence Pedigree Adult Extracellular Matrix Proteins DNA Visual Acuity Phenotype Mutation DNA Mutational Analysis Middle Aged Child Young Adult Electroretinography Exome Sequencing Adolescent Retinal Dystrophies Fluorescein Angiography Fundus Oculi East Asian People To characterize the clinical and genetic features of REEP6-associated retinopathy in 8 Japanese patients from 7 families STUDY DESIGN: Retrospective, multicenter cohort study METHODS: Biallelic REEP6 variants were identified by use of whole-exome sequencing in patients with inherited retinal dystrophy (IRD). Comprehensive ophthalmic assessments were performed in all the patients. Among a nationwide cohort of 2011 patients with IRD, 8 patients from 7 families were found to carry biallelic REEP6 variants. Four distinct variants were identified: c.223G>A, p.Glu75Lys; c.268G>C, p.Val90Leu; c.280_281del, p.Leu94ValfsTer86 (novel frameshift), and c.598+1G>A. Five families (Families 1-5) carried the compound heterozygous p.Val90Leu and c.598+1G>A variants. The other two had either homozygous c.598+1G>A (Family 6) or compound heterozygous p.Glu75Lys/p.Leu94ValfsTer86 (Family 7). In Families 1-5, the patients exhibited relatively mild phenotypes with limited to peripheral retinal degeneration in the younger patients and gradual posterior pole involvement in the older patients. Optical coherence tomography revealed well-preserved outer retinal layers at the macula, and good visual acuity was maintained even in some of the older patients. In contrast, the 2 patients in Families 6 and 7 exhibited more severe phenotypes, including macular atrophy and visual acuity decline. The combination of p.Val90Leu and c.598+1G>A variants was associated with a milder phenotype, supporting the hypothesis that p.Val90Leu is a hypomorphic variant. These findings expand the clinical and genetic spectra of REEP6-associated retinopathy, particularly among East Asian populations.
format Artículo científico
id pubmed_41553438
institution PubMed
language en
publishDate 2026
publisher Japanese journal of ophthalmology
record_format pubmed
spellingShingle Clinical and genetic characterization of REEP6-associated retinopathy in a Japanese cohort.
Tsuboi, Takeru
Mizobuchi, Kei
Yoshitake, Kazutoshi
Kuniyoshi, Kazuki
Kominami, Taro
Ueno, Shinji
Nishiguchi, Koji M
Kusaka, Shunji
Iwata, Takeshi
Hayashi, Takaaki
Nakano, Tadashi
Humans
Female
Male
Retrospective Studies
Japan
Tomography, Optical Coherence
Pedigree
Adult
Extracellular Matrix Proteins
DNA
Visual Acuity
Phenotype
Mutation
DNA Mutational Analysis
Middle Aged
Child
Young Adult
Electroretinography
Exome Sequencing
Adolescent
Retinal Dystrophies
Fluorescein Angiography
Fundus Oculi
East Asian People
Clinical and genetic characterization of REEP6-associated retinopathy in a Japanese cohort. Tsuboi, Takeru Mizobuchi, Kei Yoshitake, Kazutoshi Kuniyoshi, Kazuki Kominami, Taro Ueno, Shinji Nishiguchi, Koji M Kusaka, Shunji Iwata, Takeshi Hayashi, Takaaki Nakano, Tadashi Humans Female Male Retrospective Studies Japan Tomography, Optical Coherence Pedigree Adult Extracellular Matrix Proteins DNA Visual Acuity Phenotype Mutation DNA Mutational Analysis Middle Aged Child Young Adult Electroretinography Exome Sequencing Adolescent Retinal Dystrophies Fluorescein Angiography Fundus Oculi East Asian People To characterize the clinical and genetic features of REEP6-associated retinopathy in 8 Japanese patients from 7 families STUDY DESIGN: Retrospective, multicenter cohort study METHODS: Biallelic REEP6 variants were identified by use of whole-exome sequencing in patients with inherited retinal dystrophy (IRD). Comprehensive ophthalmic assessments were performed in all the patients. Among a nationwide cohort of 2011 patients with IRD, 8 patients from 7 families were found to carry biallelic REEP6 variants. Four distinct variants were identified: c.223G>A, p.Glu75Lys; c.268G>C, p.Val90Leu; c.280_281del, p.Leu94ValfsTer86 (novel frameshift), and c.598+1G>A. Five families (Families 1-5) carried the compound heterozygous p.Val90Leu and c.598+1G>A variants. The other two had either homozygous c.598+1G>A (Family 6) or compound heterozygous p.Glu75Lys/p.Leu94ValfsTer86 (Family 7). In Families 1-5, the patients exhibited relatively mild phenotypes with limited to peripheral retinal degeneration in the younger patients and gradual posterior pole involvement in the older patients. Optical coherence tomography revealed well-preserved outer retinal layers at the macula, and good visual acuity was maintained even in some of the older patients. In contrast, the 2 patients in Families 6 and 7 exhibited more severe phenotypes, including macular atrophy and visual acuity decline. The combination of p.Val90Leu and c.598+1G>A variants was associated with a milder phenotype, supporting the hypothesis that p.Val90Leu is a hypomorphic variant. These findings expand the clinical and genetic spectra of REEP6-associated retinopathy, particularly among East Asian populations.
title Clinical and genetic characterization of REEP6-associated retinopathy in a Japanese cohort.
topic Humans
Female
Male
Retrospective Studies
Japan
Tomography, Optical Coherence
Pedigree
Adult
Extracellular Matrix Proteins
DNA
Visual Acuity
Phenotype
Mutation
DNA Mutational Analysis
Middle Aged
Child
Young Adult
Electroretinography
Exome Sequencing
Adolescent
Retinal Dystrophies
Fluorescein Angiography
Fundus Oculi
East Asian People
url https://pubmed.ncbi.nlm.nih.gov/41553438/