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Electroretinographic abnormalities in Alport syndrome with a novel COL4A5 truncated variant (p.Try20GlyfsTer19)

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Abstract

Purpose

Alport syndrome comprises a heterogeneous group of inherited kidney diseases that are associated with ocular complications. In this study, we aimed to detail the clinical characteristics of a patient with X-linked Alport syndrome.

Methods

We performed next-generation sequencing (NGS) with hybridization capture to identify the disease-causing variant of Alport syndrome and a comprehensive ophthalmic examination, including full-field electroretinography (FF-ERG).

Results

Genetic testing using NGS with hybridization capture revealed a novel hemizygous variant [c.51_52delGA (p.Trp20GlyfsTer19)] in exon 1 of COL4A5. The patient underwent cataract surgery in both eyes because of decreased visual acuity and photophobia. The best-corrected visual acuity improved from 0.9 and 0.7 in the right and left eyes, respectively, to 1.5 in both eyes. Anterior-segment optical coherence tomography (OCT) revealed anterior and posterior lenticonus. Fundus photographs showed central and peripheral fleck retinopathy. Wide-field fundus autofluorescence (AF) imaging showed mottled hyper- and hypo-AF in the peripheral retina, which was consistent with peripheral fleck retinopathy. Furthermore, OCT revealed thinning of the inner retinal layers, especially at the temporal macular, but the outer retinal layers were preserved. Ganglion cell analysis showed no progression for 5 years. FF-ERG was performed at 41 (phakia) and 46 (pseudophakia) years of age. The amplitudes of dark-adapted (DA) and light-adapted (LA) responses showed selective b-wave abnormalities. The b/a-wave ratios of DA 3.0 were 1.22 and 1.16 in the right and left eyes, respectively. The amplitudes of DA 3.0 oscillatory potentials (OP) were reduced. Five years later, the amplitudes of DA and LA responses revealed no remarkable changes, except for an OP wave of DA 3.0, which was substantially reduced.

Conclusions

Our findings revealed electroretinographic abnormalities in a patient with Alport syndrome, which predominantly indicated impairment of the inner retina. Notably, little short-term progression was observed.

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Data availability

All data generated or analyzed during this study are included in this published article.

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Acknowledgements

We thank the patients and their families for their participation in this study. We would also like to thank Prof. Sae Ochi and Ms. Ritsuko Nakayama for assisting in the genetic analysis.

Funding

This work was supported in part by JSPS KAKENHI grant no. 21K09756.

Author information

Authors and Affiliations

  1. Department of Ophthalmology, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-Ku, Tokyo, 105-8461, Japan

    Kei Mizobuchi, Takaaki Hayashi, Ryo Ohira & Tadashi Nakano

  2. Department of Ophthalmology, Katsushika Medical Center, The Jikei University School of Medicine, Tokyo, Japan

    Takaaki Hayashi

Authors
  1. Kei Mizobuchi
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  2. Takaaki Hayashi
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  3. Ryo Ohira
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  4. Tadashi Nakano
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Contributions

All authors have contributed to the conception and design of this study. Material preparation, data collection, and analysis were performed by KM, TH, RO, and TN. The first draft of the manuscript was written by KM, and all authors commented on the previous versions of the manuscript. All authors have read and approved the final manuscript.

Corresponding author

Correspondence to Kei Mizobuchi.

Ethics declarations

Conflict of interest

Takaaki Hayashi received research funds from Alcon (Tokyo, Japan), Johnson & Johnson Vision, AMO (Tokyo, Japan), Daiichi Sankyo (Tokyo, Japan), Chugai (Tokyo, Japan), Mitsubishi Tanabe Pharma (Osaka, Japan), Senju (Osaka, Japan), Bayer (Osaka, Japan), Ritz Medical (Aichi, Japan), Uni-Hite (Kanagawa, Japan), Kuribara (Gunma, Japan), Kowa (Aichi, Japan), Kyowa Kirin (Tokyo, Japan), and Otsuka Pharma (Tokyo, Japan). The funders had no role in study design, data collection and analysis, manuscript preparation, or decision to publish.

Ethical approval

The study protocol was approved by the Institutional Review Board of the Jikei University School of Medicine (approval no. 24–231 6997). The protocol adhered to the tenets of the Declaration of Helsinki.

Statement of human rights

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

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This article does not contain any studies with animals performed by any of the authors.

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Written informed consent was obtained from the patient for publication of this case report.

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Mizobuchi, K., Hayashi, T., Ohira, R. et al. Electroretinographic abnormalities in Alport syndrome with a novel COL4A5 truncated variant (p.Try20GlyfsTer19). Doc Ophthalmol 146, 281–291 (2023). https://doi.org/10.1007/s10633-023-09935-w

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  • DOI: https://doi.org/10.1007/s10633-023-09935-w

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