Novel biallelic loss-of-function KCNV2 variants in cone dystrophy with supernormal rod responses

  • Tomoko Kutsuma
  • Satoshi Katagiri
  • Takaaki HayashiEmail author
  • Kazutoshi Yoshitake
  • Daisuke Iejima
  • Tamaki Gekka
  • Kenichi Kohzaki
  • Kei Mizobuchi
  • Yukari Baba
  • Ryo Terauchi
  • Tomokazu Matsuura
  • Shinji Ueno
  • Takeshi Iwata
  • Tadashi Nakano
Clinical Case Report



To report clinical and genetic features including long-term full-field electroretinography (FF-ERG) findings of a patient with cone dystrophy with supernormal rod responses (CDSRR).


Ophthalmological medical records including FF-ERG were retrospectively reviewed. Genetic analysis using whole-exome sequencing (WES) was performed. Identified KCNV2 variants were confirmed by Sanger sequencing.


A 30-year-old female patient was referred to our hospital for assessment of decreased vision from childhood. Funduscopy showed macular atrophy in both eyes. FF-ERG showed decreased amplitudes and delayed peak time of b-waves for dark-adapted (DA) 0.01 ERG, increased b/a-wave ratio with a slightly diminished a-wave for DA 3.0 and DA 25.7 ERG, residual a-waves and almost extinguished b-waves for light-adapted (LA) 3.0 ERG, and extremely diminished amplitudes in LA 30-Hz flicker responses. At 45 years of age, funduscopy showed progressive macular atrophy, whereas the responses for her FF-ERG remained unchanged compared to those observed at 30 years of age. WES identified the compound heterozygous KCNV2 variants (p.W67X and p.D174GfsX198) in the patient. These variants have previously been unreported as pathogenic variants. Each parent had one of the variants. Subsequently, the patient was finally diagnosed with CDSRR with the novel compound heterozygous KCNV2 variants.


Biallelic loss-of-function KCNV2 variants (p.W67X and p.D174GfsX198) were identified as the cause of CDSRR. Long-term FF-ERG findings demonstrated there were no ERG changes during 15 years of observation, indicating that there was no evidence of progressive peripheral retinal dysfunction, in spite of worsening macular atrophy.


KCNV2 Japanese Next-generation sequencing Cone dystrophy with supernormal rod response 



This work was supported by grants from the Practical Research Project for Rare/Intractable Diseases (17ek0109282h0001 for TI) from the Japan Agency for Medical Research and Development (AMED), and the Japan Society for the Promotion of Science Grant-in-Aid for Scientific Research (17K11434 and 17K11441 for TH).

Compliance with ethical standards

Conflict of interest

The authors declare that there is no conflict of interest regarding this paper.

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.

Statement on the welfare of animals

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

Informed consent

Informed consent was obtained from all participants included in the study.

Supplementary material

10633_2019_9679_MOESM1_ESM.docx (17 kb)
Supplementary material 1 (DOCX 17 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of OphthalmologyThe Jikei University School of MedicineTokyoJapan
  2. 2.Department of Ophthalmology, Katsushika Medical CenterThe Jikei University School of MedicineTokyoJapan
  3. 3.National Institute of Sensory OrgansNational Hospital Organization Tokyo Medical CenterTokyoJapan
  4. 4.Department of Laboratory MedicineThe Jikei University School of MedicineTokyoJapan
  5. 5.Department of OphthalmologyNagoya University Graduate School of MedicineNagoyaJapan

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