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Documenta Ophthalmologica

, Volume 130, Issue 1, pp 49–55 | Cite as

Novel nonsense and splice site mutations in CRB1 gene in two Japanese patients with early-onset retinal dystrophy

  • Kazuki Kuniyoshi
  • Kazuho Ikeo
  • Hiroyuki Sakuramoto
  • Masaaki Furuno
  • Kazutoshi Yoshitake
  • Yoshikazu Hatsukawa
  • Akira Nakao
  • Kazushige Tsunoda
  • Shunji Kusaka
  • Yoshikazu Shimomura
  • Takeshi Iwata
Clinical Case Report

Abstract

Purpose

To report novel mutations in the CRB1 gene in two patients with early-onset retinal dystrophy (EORD) and the longitudinal clinical course of EORD.

Patients and methods

The patients were two unrelated Japanese children. Standard ophthalmic examinations including perimetry, electroretinography, and optical coherence tomography were performed on both patients. Whole exomes of the patients and their nonsymptomatic parents were analyzed using a next-generation sequence (NGS) technique.

Results

Patient 1 was noted to have esotropia and hyperopia at age 3. His decimal best-corrected visual acuity (BCVA) was 0.6 OD and 0.3 OS at age 6 with de-pigmentation of the retinal pigment epithelium (RPE). At age 19, his central vision was still preserved; however, numerous pigment granules were present in the retina. NGS analysis revealed a p.R632X nonsense and c.652 + 1_652 + 4delGTAA splice site mutations in the CRB1 gene. Patient 2 was noted to have hyperopia at age 3. His decimal BCVA at age 6 was 0.3 OD and 0.4 OS with de-pigmented RPE. The degree of retinal pigmentation was increased but his BCVA was good until the age of 14 years. NGS analysis revealed c.652 + 1_652 + 4delGTAA and c.652 + 1_652 + 2insT splice site mutations in the CRB1 gene.

Conclusions

The phenotypes of these novel mutations for EORD are typical of CRB1-associated EORD (LCA8). They were slowly progressive until the second decade of life.

Keywords

Leber congenital amaurosis Early-onset retinal dystrophy CRB1 Optical coherence tomography Electroretinography Visual fields Japanese 

Notes

Acknowledgments

This research was supported by the research Grants to T.I., K.T., Y.S., and K.K. from the Ministry of Health, Labour and Welfare, Japan (13803661, 23164001, and 82259921), to 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 Center for Life Science Technologies.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Kazuki Kuniyoshi
    • 1
  • Kazuho Ikeo
    • 2
  • Hiroyuki Sakuramoto
    • 1
  • Masaaki Furuno
    • 3
  • Kazutoshi Yoshitake
    • 2
  • Yoshikazu Hatsukawa
    • 4
  • Akira Nakao
    • 1
  • Kazushige Tsunoda
    • 5
  • Shunji Kusaka
    • 6
  • Yoshikazu Shimomura
    • 1
  • Takeshi Iwata
    • 7
  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.Department of OphthalmologyOsaka Medical Center and Research Institute for Maternal and Child HealthOsakaJapan
  5. 5.Laboratory of Visual Physiology, National Institute of Sensory OrgansNational Hospital Organization Tokyo Medical CenterTokyoJapan
  6. 6.Department of Ophthalmology, Sakai HospitalKinki University Faculty of MedicineOsakaJapan
  7. 7.Division of Molecular and Cellular Biology, National Institute of Sensory OrgansNational Hospital Organization Tokyo Medical CenterTokyoJapan

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