Evidence map›Paper›PMID 41762300›Full record

ArticleJournal of neurology2026

Genotype-phenotype correlations in neuronal intranuclear inclusion disease-related retinopathy with CGG repeat increases in NOTCH2NLC.

Natsuko Nakamura, Kazushige Tsunoda, Akihiko Mitsutake, Shota Shibata, Miho Kawabe Matsukawa, Hiroya Naruse, Meiko Maeda, Masashi Hamada, Wataru Satake, Hiroyuki Ishiura and 3 more

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Article in Journal of neurology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

13 authors.

Natsuko NakamuraDepartment of Ophthalmology, The University of Tokyo, 7-3-1 Hongo Bunkyo-Ku, Tokyo, 113-8655, Japan. nakamura-ntk@umin.ac.jp.ORCID http://orcid.org/0000-0001-5113-0428
Kazushige TsunodaDivision of Vision Research, National Institute of Sensory Organs, NHO Tokyo Medical Center, 2-5-1 Higashigaoka, Meguro-Ku, Tokyo, 152-8902, Japan.
Akihiko MitsutakeDepartment of Neurology, The University of Tokyo, 7-3-1 Hongo Bunkyo-Ku, Tokyo, 113-8655, Japan.
Shota ShibataDepartment of Neurology, The University of Tokyo, 7-3-1 Hongo Bunkyo-Ku, Tokyo, 113-8655, Japan.
Miho Kawabe MatsukawaDepartment of Neurology, The University of Tokyo, 7-3-1 Hongo Bunkyo-Ku, Tokyo, 113-8655, Japan.
Hiroya NaruseDepartment of Neurology, The University of Tokyo, 7-3-1 Hongo Bunkyo-Ku, Tokyo, 113-8655, Japan.
Meiko MaedaDepartment of Neurology, The University of Tokyo, 7-3-1 Hongo Bunkyo-Ku, Tokyo, 113-8655, Japan.
Masashi HamadaDepartment of Neurology, The University of Tokyo, 7-3-1 Hongo Bunkyo-Ku, Tokyo, 113-8655, Japan.
Wataru SatakeDepartment of Neurology, The University of Tokyo, 7-3-1 Hongo Bunkyo-Ku, Tokyo, 113-8655, Japan.
Hiroyuki IshiuraDepartment of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikatacho, Kita Ward, Okayama, 700-0914, Japan.
Shoji TsujiDepartment of Neurology, The University of Tokyo, 7-3-1 Hongo Bunkyo-Ku, Tokyo, 113-8655, Japan.
Tatsushi TodaDepartment of Neurology, The University of Tokyo, 7-3-1 Hongo Bunkyo-Ku, Tokyo, 113-8655, Japan.
Hiromasa SawamuraDepartment of Ophthalmology, The University of Tokyo, 7-3-1 Hongo Bunkyo-Ku, Tokyo, 113-8655, Japan.

Funding

Japan Agency for Medical Research and Development JP19ek0109279Japan Agency for Medical Research and Development JP22ek0109491Japan Agency for Medical Research and Development JP23ek0109673Japan Society for the Promotion of Science JP20H03588Japan Society for the Promotion of Science JP23K09022Japan Society for the Promotion of Science JP23K27514
6 · The paper itself

Abstract

backgroundTo report the genotype-phenotype correlations in neuronal intranuclear inclusion disease (NIID)-related retinopathy.

methods13 patients from 12 families (62-81 years) clinically diagnosed with late-onset NIID were studied. Best-corrected visual acuity (BCVA), Goldmann perimetry, fundus photography, fundus autofluorescence (FAF), optical coherence tomography (OCT), and full-field electroretinography (ERGs) were examined. The number of CGG repeats in NOTCH2NLC was determined. Genotype-phenotype correlations between the number of CGG repeats and the age at onset of ocular symptoms, disease duration, ellipsoid zone (EZ) length of photoreceptors in the peripapillary area, and ERGs amplitudes were determined.

resultsAll patients had expanded CGG repeats (100-177 repeat units) in the NOTCH2NLC, and 11 patients noticed ocular symptoms before cognitive decline and two noticed them in their 20 s. FAF decrease and EZ absence in the peripapillary area were observed in all cases. ERGs indicated rod-cone dysfunction. The number of repeats was significantly correlated with an amplitude of all components of scotopic and photopic ERGs except for the b-wave in dark-adapted (DA) 0.01 and DA 10.0 ERGs. The highest coefficient of correlation was found between the amplitudes of the d-wave, a-wave, and the b-wave in light-adapted (LA) ON-OFF ERG (ρ = -0.97, P < 0.001, ρ = -0.92, P < 0.01, ρ = -0.84, P < 0.01 respectively), the b-wave in LA 3.0 (ρ = -0.75, P < 0.01), and 30 Hz flicker (ρ = -0.71, P < 0.05).

conclusionsExpanded CGG repeats in NOTCH2NLC develop ocular symptoms earlier than reported. The number of repeats can be a biomarker for the severity of retinal dysfunction in NIID-related retinopathy.

Indexed as

Neurodegenerative DiseasesRetinal DiseasesTrinucleotide Repeat ExpansionAgedAged, 80 and overElectroretinographyFemaleGenetic Association StudiesHumansIntercellular Signaling Peptides and ProteinsIntranuclear Inclusion BodiesMaleMiddle AgedNerve Tissue ProteinsTomography, Optical CoherenceIntercellular Signaling Peptides and ProteinsNerve Tissue ProteinsNOTCH2NLC protein, humanERGsGenotype–phenotype correlationsNIIDNOTCH2NLCRetinopathyTriplet repeat

Identifiers

PMID41762300

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.