Documenta Ophthalmologica

, Volume 128, Issue 3, pp 219–228 | Cite as

Longitudinal clinical course of three Japanese patients with Leber congenital amaurosis/early-onset retinal dystrophy with RDH12 mutation

  • Kazuki Kuniyoshi
  • Hiroyuki Sakuramoto
  • Kazutoshi Yoshitake
  • Kosuke Abe
  • Kazuho Ikeo
  • Masaaki Furuno
  • Kazushige Tsunoda
  • Shunji Kusaka
  • Yoshikazu Shimomura
  • Takeshi Iwata
Clinical Case Report
First Online:
Received:
Accepted:

Abstract

Purpose

To report the longitudinal clinical course of three Japanese patients from two families with Leber congenital amaurosis/early-onset retinal dystrophy (LCA/EORD), and the results of next-generation DNA sequences on them.

Patients and methods

The patients were three Japanese children: a 4-year-old girl, a 6-year-old boy, and a 3-year-old girl. Patients 1 and 2 were siblings, and patient 3 was from an unrelated family. Standard ophthalmic examinations including perimetry, electroretinography, optical coherence tomography, and ultrasonography were performed on each patient. The patients were observed for 28, 16, and 10 years. Whole exomes of the patients and their non-symptomatic parents were analyzed using a next-generation sequence technique.

Results

The decimal visual acuity varied between 0.07 and 0.6 at the initial visit and decreased to counting finger to hand motion in their teens. Funduscopy showed diffuse retinal and macular degeneration. During the follow-up period, a posterior staphyloma developed and the macular area became atrophic. Patient 1 developed cataracts in her early twenties. Genetic analysis revealed a homozygous A126V substitution in the RDH12 gene in all patients.

Conclusions

The three patients with LCA/EORD had a progressive decrease of their vision with the formation of a posterior staphyloma. This is the first report of Japanese patients with LCA/EORD with a RDH12 mutation.

Keywords

Leber congenital amaurosis Early-onset retinal dystrophy RDH12 Macular dystrophy Posterior staphyloma Electroretinogram Next-generation sequence analysis 
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Notes

Acknowledgments

Authors express gratitude to Professor Toshifumi Otori, M.D., who transferred the longitudinal clinical data to us and gave us suggestive advice on this study. The authors wish to acknowledge RIKEN GeNAS for the sequencing of the Exome enriched libraries. This research was supported by the research grants to T.I. and K.K. from the Ministry of Health, Labour and Welfare, Japan (13803661), to K.T. and K.K. from the Ministry of Health, Labour and Welfare, Japan (23164001), Y.S from the Ministry of Health, Labour and Welfare, Japan (82259921), S.K. and K.K. from Japan Society for the Promotion of Science, Japan (23592597), and to M.F. from the Japanese Ministry of Education, Culture, Sports, Science and Technology (MEXT) for RIKEN Omics Science Center.

Conflict of interest

All authors have no commercial interests related to this research.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Kazuki Kuniyoshi
    • 1
  • Hiroyuki Sakuramoto
    • 1
  • Kazutoshi Yoshitake
    • 2
  • Kosuke Abe
    • 1
  • Kazuho Ikeo
    • 2
  • Masaaki Furuno
    • 3
  • Kazushige Tsunoda
    • 4
  • Shunji Kusaka
    • 5
  • Yoshikazu Shimomura
    • 1
  • Takeshi Iwata
    • 6
  1. 1.Department of OphthalmologyKinki University Faculty of MedicineOsaka-Sayama CityJapan
  2. 2.Laboratory of DNA Data AnalysisNational Institute of GeneticsShizuokaJapan
  3. 3.Transcriptome Technology Team, Life Science Accelerator Technology Group, Division of Genomic TechnologiesRIKEN Center for Life Science TechnologiesYokohamaJapan
  4. 4.Laboratory of Visual Physiology, National Institute of Sensory OrgansNational Hospital Organization Tokyo Medical CenterTokyoJapan
  5. 5.Department of Ophthalmology, Sakai HospitalKinki University Faculty of MedicineSakai City, OsakaJapan
  6. 6.Division of Molecular and Cellular Biology, National Institute of Sensory OrgansNational Hospital Organization Tokyo Medical CenterTokyoJapan

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