Skip to main content

Advertisement

SpringerLink
Log in

Oguchi disease caused by a homozygous novel SAG splicing alteration associated with the multiple evanescent white dot syndrome: A 15-month follow-up

  • Original Research Article
  • Published:
Documenta Ophthalmologica Aims and scope Submit manuscript

Abstract

Purpose

We report a 15-month follow-up case on a Chinese patient with Oguchi disease associated with the multiple evanescent white dot syndrome (MEWDS).

Methods

The patient’s clinical presentation and follow-up visits were documented via decimal best-corrected visual acuity, fundus photography, fundus autofluorescence (FAF) imaging, near-infrared FAF, spectral domain optical coherence tomography, Humphrey’s visual fields, microperimetry, and multifocal electroretinography. We also performed whole exome sequencing for screening variation in the patient and her relatives.

Results

The patient had typical clinical characteristic of Oguchi disease, including night blindness, the Mizuo–Nakamura phenomenon (a golden yellow discoloration of the fundus that disappears in the prolonged dark adaptation [DA]) and typical full-field electroretinogram changes (nearly undetected b-wave in 0.01 and 0.03 ERGs that can partially recover only after prolonged DA). Aside from Oguchi disease, the patient was also diagnosed with the MEWDS based on clinical detections, including suddenly reduced visual acuity, appeared white dots, blurred ellipsoid zone and disrupted interdigitation zone, enlarged blind spot, and reduced macular sensitivity. A series of investigations revealed that along with the 15-month follow-up after onset, the visual acuity enhanced, the numerous white dots disappeared, and the macular structure returned to normal. Moreover, the novel homozygous splicing alteration c.181 + 1G > A was identified in the SAG gene.

Conclusions

This work is the first long-term case study of a patient with Oguchi disease associated with the MEWDS. The recovery period of symptoms caused by the MEWDS was much longer than that in typical patients with MEWDS. Molecular genetics demonstrate that this is the first case of Oguchi disease caused by splicing alterations in the SAG gene.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Fuchs S, Nakazawa M, Maw M, Tamai M, Oguchi Y, Gal A (1995) A homozygous 1-base pair deletion in the arrestin gene is a frequent cause of Oguchi disease in Japanese. Nat Genet 10(3):360

    Article  CAS  PubMed  Google Scholar 

  2. Miyake Y, Horiguchi M, Suzuki S, Kondo M, Tanikawa A (1996) Electrophysiological findings in patients with Oguchi’s disease. Jpn J Ophthalmol 40(4):511–519

    CAS  PubMed  Google Scholar 

  3. Godara P, Cooper RF, Sergouniotis PI, Diederichs MA, Streb MR, Genead MA et al (2012) Assessing retinal structure in complete congenital stationary night blindness and Oguchi disease. Am J Ophthalmol 154(6):987-1001.e1

    Article  PubMed  PubMed Central  Google Scholar 

  4. Yamamoto S, Sippel KC, Berson EL, Dryja TP (1997) Defects in the rhodopsin kinase gene in the Oguchi form of stationary night blindness. Nat Genet 15(2):175

    Article  CAS  PubMed  Google Scholar 

  5. dell’Omo R, Pavesio CE (2012) Multiple evanescent white dot syndrome (MEWDS). Int Ophthalmol Clin 52(4):221–228

    Article  PubMed  Google Scholar 

  6. Brydak-Godowska J, Golebiewska J, Turczynska M, Moneta-Wielgos J, Samsel A, Borkowski PK et al (2017) Observation and clinical pattern in patients with white dot syndromes: the role of color photography in monitoring ocular changes in long-term observation. Med Sci Monit: Int Med J Exp Clin Res 23:1106–1115

    Article  Google Scholar 

  7. McCulloch DL, Marmor MF, Brigell MG, Hamilton R, Holder GE, Tzekov R et al (2015) ISCEV Standard for full-field clinical electroretinography (2015 update). Doc Ophthalmol 130(1):1–12

    Article  PubMed  Google Scholar 

  8. Hood DC, Bach M, Brigell M, Keating D, Kondo M, Lyons JS et al (2012) ISCEV standard for clinical multifocal electroretinography (mfERG) (2011 edition). Doc Ophthalmol 124(1):1–13

    Article  PubMed  Google Scholar 

  9. Sergouniotis PI, Davidson AE, Sehmi K, Webster AR, Robson AG, Moore AT (2011) Mizuo–Nakamura phenomenon in Oguchi disease due to a homozygous nonsense mutation in the SAG gene. Eye (London, England). 25(8):1098–1101

    Article  CAS  PubMed Central  Google Scholar 

  10. Nishiguchi KM, Ikeda Y, Fujita K, Kunikata H, Akiho M, Hashimoto K et al (2019) Phenotypic features of Oguchi disease and retinitis pigmentosa in patients with S-antigen mutations: a long-term follow-up study. Ophthalmology 126:1557–1566

    Article  PubMed  Google Scholar 

  11. Yuan A, Nusinowitz S, Sarraf D (2011) Mizuo-Nakamura phenomenon with a negative waveform ERG. Br J Ophthalmol 95(1):147–148

    Article  CAS  PubMed  Google Scholar 

  12. Agarwal R, Tripathy K, Bandyopadhyay G, Basu K (2019) Mizuo–Nakamura phenomenon in an Indian male. Clin Case Rep 7(2):401–403

    Article  PubMed  PubMed Central  Google Scholar 

  13. Colombo L, Abeshi A, Maltese PE, Frecer V, Miertus J, Cerra D et al (2018) Oguchi type I caused by a homozygous missense variation in the SAG gene. Eur J Med Genet 62:103548

    Article  PubMed  Google Scholar 

  14. Huang L, Li W, Tang W, Zhu X, Ou-Yang P, Lu G (2012) A Chinese family with Oguchi’s disease due to compound heterozygosity including a novel deletion in the arrestin gene. Mol Vis 18:528–536

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Kuroda M, Hirami Y, Nishida A, Jin ZB, Ishigami C, Takahashi M et al (2011) A case of Oguchi disease with disappearance of golden tapetal-like fundus reflex after vitreous resection. Nippon Ganka Gakkai Zasshi 115(10):916–923

    PubMed  Google Scholar 

  16. Fujinami K, Tsunoda K, Nakamura M, Oguchi Y, Miyake Y (2011) Oguchi disease with unusual findings associated with a heterozygous mutation in the SAG gene. Arch Ophthalmol (Chicago, IL: 1960) 129(10):1375–1376

    Article  Google Scholar 

  17. Maw M, Kumaramanickavel G, Kar B, John S, Bridges R, Denton M (1998) Two Indian siblings with Oguchi disease are homozygous for an arrestin mutation encoding premature termination. Hum Mutat 50(Suppl 1):S317–S319

    Article  Google Scholar 

  18. Hayashi T, Tsuzuranuki S, Kozaki K, Urashima M, Tsuneoka H (2011) Macular dysfunction in Oguchi disease with the frequent mutation 1147delA in the SAG gene. Ophthalmic Res 46(4):175–180

    Article  CAS  PubMed  Google Scholar 

  19. Zhang Q, Zulfiqar F, Riazuddin SA, Xiao X, Yasmeen A, Rogan PK et al (2005) A variant form of Oguchi disease mapped to 13q34 associated with partial deletion of GRK1 gene. Mol Vis 11:977–985

    CAS  PubMed  Google Scholar 

  20. Jampol LM, Sieving PA, Pugh D, Fishman GA, Gilbert H (1984) Multiple evanescent white dot syndrome: I. Clinical findings. Arch Ophthalmol 102(5):671–674

    Article  CAS  PubMed  Google Scholar 

  21. Cahuzac A, Wolff B, Mathis T, Errera MH, Sahel JA, Mauget-Faysse M (2017) Multimodal imaging findings in ‘hyper-early’ stage MEWDS. Br J Ophthalmol 101(10):1381–1385

    Article  PubMed  Google Scholar 

  22. Furino C, Boscia F, Cardascia N, Alessio G, Sborgia C (2009) Fundus autofluorescence and multiple evanescent white dot syndrome. Retina 29(1):60–63

    Article  PubMed  Google Scholar 

  23. Margolis R, Mukkamala SK, Jampol LM, Spaide RF, Ober MD, Sorenson JA et al (2011) The expanded spectrum of focal choroidal excavation. Arch Ophthalmol 129(10):1320–1325

    Article  PubMed  Google Scholar 

  24. Mantovani A, Invernizzi A, Staurenghi G, Herbort CP Jr (2019) Multiple evanescent white dot syndrome: a multimodal imaging study of foveal granularity. Ocular Immunol Inflamm 27(1):141–147

    Article  Google Scholar 

  25. Hashimoto Y, Saito W, Hasegawa Y, Noda K, Ishida S (2019) Involvement of inner choroidal layer in choroidal thinning during regression of multiple evanescent white dot syndrome. J Ophthalmol 2019:6816925

    Article  PubMed  PubMed Central  Google Scholar 

  26. Yang JS, Chen CL, Hu YZ, Zeng R (2018) Multiple evanescent white dot syndrome following rabies vaccination: a case report. BMC Ophthalmol 18(1):312

    Article  PubMed  PubMed Central  Google Scholar 

  27. Yang CS, Wang AG, Lin YH, Huang YM, Lee FL, Lee SM (2012) Optical coherence tomography in resolution of photoreceptor damage in multiple evanescent white dot syndrome. J Chin Med Assoc: JCMA 75(12):663–666

    Article  PubMed  Google Scholar 

  28. Marsiglia M, Gallego-Pinazo R, De Souza EC, Munk MR, Yu S, Mrejen S et al (2016) Expanded clinical spectrum of multiple evanescent white dot syndrome with multimodal imaging. Retina 36(1):64–74

    Article  PubMed  Google Scholar 

  29. Li D, Kishi S (2009) Restored photoreceptor outer segment damage in multiple evanescent white dot syndrome. Ophthalmology 116(4):762–770

    Article  PubMed  Google Scholar 

  30. Jampol LM, Becker KG (2003) White spot syndromes of the retina: a hypothesis based on the common genetic hypothesis of autoimmune/inflammatory disease. Am J Ophthalmol 135(3):376–379

    Article  PubMed  Google Scholar 

  31. Gass JD (2003) Are acute zonal occult outer retinopathy and the white sopt syndromes (AZOOR complex) specific autoimmune diseases? Am J Ophthalmol 135:380–381

    Article  PubMed  Google Scholar 

  32. Yamada T, Matsumoto M, Kadoi C, Nagaki Y, Hayasaka Y, Hayasaka S, Hayasaka S (1999) 1147 del A mutation in the arrestin gene in Japanese patients with Oguchi disease. Ophthalmic Genet 20(2):117–120

    Article  CAS  PubMed  Google Scholar 

  33. Nakamachi Y, Nakamura M, Fujii S, Yamamoto M, Okubo K (1998) Oguchi disease with sectoral retinitis pigmentosa harboring adenine deletion at position 1147 in the arrestin gene. Am J Ophthalmol 125(2):249–251

    Article  CAS  PubMed  Google Scholar 

  34. Nakazawa M, Wada Y, Fuchs S, Gal A, Tamai M (1997) Oguchi disease: phenotypic characteristics of patients with the frequent 1147delA mutation in the arrestin gene. Retina (Philadelphia, PA) 17(1):17–22

    Article  CAS  Google Scholar 

  35. Waheed NK, Qavi AH, Malik SN, Maria M, Riaz M, Cremers FP et al (2012) A nonsense mutation in S-antigen (p.Glu306*) causes Oguchi disease. Mol Vis 18:1253–1259

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

Kaoru Fujinami is a paid consultant of Astellas Pharma Inc, Kubota Pharmaceutical Holdings Co., Ltd, and Acucela Inc. Kaoru Fujinami reports personal fees from Astellas Pharma Inc, personal fees from Kubota Pharmaceutical Holdings Co., Ltd., personal fees from Acucela Inc., personal fees from SANTEN Company Limited, personal fees from Foundation Fighting Blindness, personal fees from Foundation Fighting Blindness Clinical Research Institute, personal fees from Japanese Ophthalmology Society, personal fees from Japan Retinitis Pigmentosa Society. Kaoru Fujinami reports grants from Astellas Pharma Inc (NCT03281005), outside the submitted work.

Author information

Author notes

  1. Co-first authors: Xiao Liu and Lixia Gao

Authors and Affiliations

  1. Southwest Hospital/Southwest Eye Hospital, Third Military Medical University (Army Medical University), No. 30 Gaotanyan Street Shapingba District, Chongqing, China

    Xiao Liu, Lixia Gao, Gang Wang, Yanling Long, Jiayun Ren, Xiaohong Meng & Shiying Li

  2. Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Chongqing, China

    Xiao Liu, Lixia Gao, Gang Wang, Yanling Long, Jiayun Ren, Xiaohong Meng & Shiying Li

  3. Laboratory of Visual Physiology, Division for Vision Research, National Institute of Sensory Organs, National Hospital Organization, Tokyo Medical Center, Tokyo, Japan

    Xiao Liu

  4. Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan

    Xiao Liu & Kaoru Fujinami

  5. Department of Genetics, UCL Institute of Ophthalmology, London, UK

    Kaoru Fujinami

  6. Division of Inherited Eye Diseases, Moorfields Eye Hospital, London, UK

    Kaoru Fujinami

Authors
  1. Xiao Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lixia Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gang Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yanling Long
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jiayun Ren
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kaoru Fujinami
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xiaohong Meng
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Shiying Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Shiying Li is supported by grants from the National Nature Science Foundation of China (81974138), Third Military Medical University (Army Medical University) research grant (2017XYY02), and National Basic Research Program of China (2018YFA0107301). Gang Wang is supported by grants from the Third Military Medical University, Southwest Hospital Innovation Grant (SWH2015LC15). Kaoru Fujinami is supported by grants from Grant-in-Aid for Young Scientists (A) of the Ministry of Education, Culture, Sports, Science and Technology, Japan (16H06269), grants from Grant-in-Aid for Scientists to support international collaborative studies of the Ministry of Education, Culture, Sports, Science and Technology, Japan (16KK01930002), grants from National Hospital Organization Network Research Fund (H30-NHO-2-12), grants from the Foundation for Fighting Blindness–Alan Laties Career Development Program (CF-CL-0416-0696-UCL), grants from Health Labor Sciences Research Grant, The Ministry of Health, Labor and Welfare (201711107A), and grants from the Great Britain Sasakawa Foundation Butterfield Awards.

Corresponding authors

Correspondence to Xiaohong Meng or Shiying Li.

Ethics declarations

Conflict of interest

All authors have completed the COI Form for Disclosure of Potential Conflicts of Interest. Individual investigators who participate in the sponsored project(s) are not directly compensated by the sponsor but may receive a salary or other support from the institution to support their effort on the project(s).

Statements of human rights

The procedures used were approved by the local ethics committee of Southwest Eye Hospital, Third Military Medical University (Army Medical University), Chongqing, China (reference number: 73981486-2), and all procedures were performed in accordance with the Declaration of Helsinki.

Informed consent

The patient and her relatives, who were also studied upon, gave informed consent for all procedures described involved in the study.

Statement on the welfare of animals

All the experimental procedures were performed in accordance with institutional animal welfare guidelines, were approved by the Third Military Medical University Animal Care and Use Committee

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, X., Gao, L., Wang, G. et al. Oguchi disease caused by a homozygous novel SAG splicing alteration associated with the multiple evanescent white dot syndrome: A 15-month follow-up. Doc Ophthalmol 141, 217–226 (2020). https://doi.org/10.1007/s10633-020-09766-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10633-020-09766-z

Keywords

Search

Navigation