Tags

Type your tag names separated by a space and hit enter

NOTCH2NLC GGC repeat expansion causes retinal pathology with intranuclear inclusions throughout the retina and causes visual impairment.
Acta Neuropathol Commun. 2023 05 02; 11(1):71.AN

Abstract

The retinal pathology of genetically confirmed neuronal intranuclear inclusion disease (NIID) is yet unknown. We report the ocular findings in four NIID patients with NOTCH2NLC GGC repeat expansion to investigate the pathology of retinopathy. All four NIID patients were diagnosed by skin biopsy and NOTCH2NLC GGC repeat analysis. Ocular findings in patients with NIID were studied using fundus photographs, optical coherence tomographic images (OCT), and full-field electroretinograms (ERGs). The histopathology of the retina was studied on autopsy samples from two cases with immunohistochemistry. All patients had an expansion of the GGC repeat (87-134 repeats) in the NOTCH2NLC. Two patients were legally blind and had been diagnosed with retinitis pigmentosa prior to the diagnosis of NIID and assessed with whole exome sequencing to rule out comorbidity with other retinal diseases. Fundus photographs around the posterior pole showed chorioretinal atrophy in the peripapillary regions. OCT showed thinning of the retina. ERGs showed various abnormalities in cases. The histopathology of autopsy samples showed diffusely scattered intranuclear inclusions throughout the retina from the retinal pigment epithelium to the ganglion cell layer, and optic nerve glial cells. And severe gliosis was observed in retina and optic nerve. The NOTCH2NLC GGC repeat expansion causes numerous intranuclear inclusions in the retina and optic nerve cells and gliosis. Visual dysfunction could be the first sign of NIID. We should consider NIID as one of the causes of retinal dystrophy and investigate the GGC repeat expansion in NOTCH2NLC.

Links

PMC Free PDF

Authors+Show Affiliations

Sone J
Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University, 1-1 Yazakokarimata, Nagakute, Aichi, 480-1195, Japan. jsone@aichi-med-u.ac.jp. Department of Neurology, National Hospital Organization Nagoya Medical Center, 4-1-1, Sannomaru, Naka-Ku, Nagoya, Aichi, 460-0001, Japan. jsone@aichi-med-u.ac.jp. Department of Neurology, National Hospital Organization Suzuka National Hospital, 3-2-1, Kasado, Suzuka, Mie, 513-8501, Japan. jsone@aichi-med-u.ac.jp. Department of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-Ku, Nagoya, Aichi, 466-8560, Japan. jsone@aichi-med-u.ac.jp.
Ueno S
Department of Ophthalmology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-Ku, Nagoya, Aichi, 466-8560, Japan. Department of Ophthalmology, Hirosaki University Graduate School of Medicine, 5 Zaifu, Hirosaki, Aomori, 036-8562, Japan.
Akagi A
Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University, 1-1 Yazakokarimata, Nagakute, Aichi, 480-1195, Japan.
Miyahara H
Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University, 1-1 Yazakokarimata, Nagakute, Aichi, 480-1195, Japan.
Tamai C
Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University, 1-1 Yazakokarimata, Nagakute, Aichi, 480-1195, Japan.
Riku Y
Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University, 1-1 Yazakokarimata, Nagakute, Aichi, 480-1195, Japan. Department of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-Ku, Nagoya, Aichi, 466-8560, Japan.
Yabata H
Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University, 1-1 Yazakokarimata, Nagakute, Aichi, 480-1195, Japan. Department of Neurology, Shiga University of Medical Science. Seta-Tsukinowa, Otsu, 520-2192, Japan.
Koizumi R
Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University, 1-1 Yazakokarimata, Nagakute, Aichi, 480-1195, Japan. Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine, 22-2 Seto, Kanazawa-Ku, Yokohama, Kanagawa, 236-0027, Japan.
Hattori T
Department of Ophthalmology, National Hospital Organization Nagoya Medical Center, 4-1-1, Sannomaru, Naka-Ku, Nagoya, Aichi, 460-0001, Japan.
Hirose H
Department of Ophthalmology, National Hospital Organization Nagoya Medical Center, 4-1-1, Sannomaru, Naka-Ku, Nagoya, Aichi, 460-0001, Japan.
Koyanagi Y
Department of Ophthalmology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-Ku, Nagoya, Aichi, 466-8560, Japan. Department of Ophthalmology, National Hospital Organization Nagoya Medical Center, 4-1-1, Sannomaru, Naka-Ku, Nagoya, Aichi, 460-0001, Japan.
Kobayashi R
Department of Neurology, National Hospital Organization Nagoya Medical Center, 4-1-1, Sannomaru, Naka-Ku, Nagoya, Aichi, 460-0001, Japan.
Okada H
Department of Neurology, National Hospital Organization Nagoya Medical Center, 4-1-1, Sannomaru, Naka-Ku, Nagoya, Aichi, 460-0001, Japan.
Kishimoto Y
Department of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-Ku, Nagoya, Aichi, 466-8560, Japan.
Hashizume Y
Department of Neuropathology, Choju Medical Institute, Fukushimura Hospital, 19-14, Yamanaka, Noyori, Toyohashi, Aichi, 441-8124, Japan.
Sobue G
Department of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-Ku, Nagoya, Aichi, 466-8560, Japan. Aichi Medical University, 1-1 Yazakokarimata, Nagakute, Aichi, 480-1195, Japan.
Yoshida M
Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University, 1-1 Yazakokarimata, Nagakute, Aichi, 480-1195, Japan.
Iwasaki Y
Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University, 1-1 Yazakokarimata, Nagakute, Aichi, 480-1195, Japan.

MeSH

HumansGliosisIntranuclear Inclusion BodiesNeurodegenerative DiseasesRetinaReceptor, Notch2

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

37131242

Citation

Sone, Jun, et al. "NOTCH2NLC GGC Repeat Expansion Causes Retinal Pathology With Intranuclear Inclusions Throughout the Retina and Causes Visual Impairment." Acta Neuropathologica Communications, vol. 11, no. 1, 2023, p. 71.
Sone J, Ueno S, Akagi A, et al. NOTCH2NLC GGC repeat expansion causes retinal pathology with intranuclear inclusions throughout the retina and causes visual impairment. Acta Neuropathol Commun. 2023;11(1):71.
Sone, J., Ueno, S., Akagi, A., Miyahara, H., Tamai, C., Riku, Y., Yabata, H., Koizumi, R., Hattori, T., Hirose, H., Koyanagi, Y., Kobayashi, R., Okada, H., Kishimoto, Y., Hashizume, Y., Sobue, G., Yoshida, M., & Iwasaki, Y. (2023). NOTCH2NLC GGC repeat expansion causes retinal pathology with intranuclear inclusions throughout the retina and causes visual impairment. Acta Neuropathologica Communications, 11(1), 71. https://doi.org/10.1186/s40478-023-01564-3
Sone J, et al. NOTCH2NLC GGC Repeat Expansion Causes Retinal Pathology With Intranuclear Inclusions Throughout the Retina and Causes Visual Impairment. Acta Neuropathol Commun. 2023 05 2;11(1):71. PubMed PMID: 37131242.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - NOTCH2NLC GGC repeat expansion causes retinal pathology with intranuclear inclusions throughout the retina and causes visual impairment. AU - Sone,Jun, AU - Ueno,Shinji, AU - Akagi,Akio, AU - Miyahara,Hiroaki, AU - Tamai,Chisato, AU - Riku,Yuichi, AU - Yabata,Hiroyuki, AU - Koizumi,Ryuichi, AU - Hattori,Tomohiro, AU - Hirose,Hiroshi, AU - Koyanagi,Yoshito, AU - Kobayashi,Rei, AU - Okada,Hisashi, AU - Kishimoto,Yoshiyuki, AU - Hashizume,Yoshio, AU - Sobue,Gen, AU - Yoshida,Mari, AU - Iwasaki,Yasushi, Y1 - 2023/05/02/ PY - 2023/02/19/received PY - 2023/04/10/accepted PY - 2023/5/4/medline PY - 2023/5/3/pubmed PY - 2023/5/2/entrez KW - Diffusion weighted image KW - GGC repeat KW - Gliosis KW - Leukoencephalopathy KW - NOTCH2NLC KW - Neuronal intranuclear inclusion disease KW - Retinal pathology KW - Retinitis Pigmentosa KW - p-62 SP - 71 EP - 71 JF - Acta neuropathologica communications JO - Acta Neuropathol Commun VL - 11 IS - 1 N2 - The retinal pathology of genetically confirmed neuronal intranuclear inclusion disease (NIID) is yet unknown. We report the ocular findings in four NIID patients with NOTCH2NLC GGC repeat expansion to investigate the pathology of retinopathy. All four NIID patients were diagnosed by skin biopsy and NOTCH2NLC GGC repeat analysis. Ocular findings in patients with NIID were studied using fundus photographs, optical coherence tomographic images (OCT), and full-field electroretinograms (ERGs). The histopathology of the retina was studied on autopsy samples from two cases with immunohistochemistry. All patients had an expansion of the GGC repeat (87-134 repeats) in the NOTCH2NLC. Two patients were legally blind and had been diagnosed with retinitis pigmentosa prior to the diagnosis of NIID and assessed with whole exome sequencing to rule out comorbidity with other retinal diseases. Fundus photographs around the posterior pole showed chorioretinal atrophy in the peripapillary regions. OCT showed thinning of the retina. ERGs showed various abnormalities in cases. The histopathology of autopsy samples showed diffusely scattered intranuclear inclusions throughout the retina from the retinal pigment epithelium to the ganglion cell layer, and optic nerve glial cells. And severe gliosis was observed in retina and optic nerve. The NOTCH2NLC GGC repeat expansion causes numerous intranuclear inclusions in the retina and optic nerve cells and gliosis. Visual dysfunction could be the first sign of NIID. We should consider NIID as one of the causes of retinal dystrophy and investigate the GGC repeat expansion in NOTCH2NLC. SN - 2051-5960 UR - https://www.unboundmedicine.com/medline/citation/37131242/NOTCH2NLC_GGC_repeat_expansion_causes_retinal_pathology_with_intranuclear_inclusions_throughout_the_retina_and_causes_visual_impairment_ DB - PRIME DP - Unbound Medicine ER -