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Development of a molecular diagnostic test for Retinitis Pigmentosa in the Japanese population

  • Clinical Investigation
  • Published:
Japanese Journal of Ophthalmology Aims and scope Submit manuscript

Abstract

Purpose

Retinitis Pigmentosa (RP) is the most common form of inherited retinal dystrophy caused by different genetic variants. More than 60 causative genes have been identified to date. The establishment of cost-effective molecular diagnostic tests with high sensitivity and specificity can be beneficial for patients and clinicians. Here, we developed a clinical diagnostic test for RP in the Japanese population.

Study design

Evaluation of diagnostic technology, Prospective, Clinical and experimental study.

Methods

A panel of 39 genes reported to cause RP in Japanese patients was established. Next generation sequence (NGS) technology was applied for the analyses of 94 probands with RP and RP-related diseases. After interpretation of detected genetic variants, molecular diagnosis based on a study of the genetic variants and a clinical phenotype was made by a multidisciplinary team including clinicians, researchers and genetic counselors.

Results

NGS analyses found 14,343 variants from 94 probands. Among them, 189 variants in 83 probands (88.3% of all cases) were selected as pathogenic variants and 64 probands (68.1%) have variants which can cause diseases. After the deliberation of these 64 cases, molecular diagnosis was made in 43 probands (45.7%). The final molecular diagnostic rate with the current system combining supplemental Sanger sequencing was 47.9% (45 of 94 cases).

Conclusions

The RP panel provides the significant advantage of detecting genetic variants with a high molecular diagnostic rate. This type of race-specific high-throughput genotyping allows us to conduct a cost-effective and clinically useful genetic diagnostic test.

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Acknowledgements

The authors thank all individuals who participated in this study. We are also thankful to Dr. Elias I. Traboulsi (Cleveland Clinic, Cleveland, OH, USA), Yumie Hiraoka (RIKEN), Midori Yamamoto, Sachiko Ohta and Keiko Tanaka (Institute of Biomedical Research and Innovation Hospital), Elliot Choi and Susie Suh (Case Western Reserve University) and members of the Takahashi laboratory for their comments and technical support. This work was supported by the JSPS KAKENHI Grant (JPKAKEN 16H07505) (AM) and the AMED Highway Program for Realization of Regenerative Medicine (MT).

Author information

Authors and Affiliations

  1. Laboratory for Retinal Regeneration, RIKEN Center for Developmental Biology, 2-2-3 Minatojimaminamimachi, Chuo-ku, Kobe, Hyogo, 650-0047, Japan

    Akiko Maeda, Akiko Yoshida, Kanako Kawai, Yuki Arai, Ryutaro Akiba, Akira Inaba & Masayo Takahashi

  2. Division of Ophthalmology, Institute of Biomedical Research and Innovation Hospital, Kobe, Japan

    Akiko Maeda, Akiko Yoshida, Seiji Takagi, Yasuhiko Hirami, Yasuo Kurimoto & Masayo Takahashi

  3. Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, USA

    Akiko Maeda

  4. Department of Ophthalmology, Kobe City Medical Center General Hospital, Kobe, Japan

    Seiji Takagi, Yasuhiko Hirami, Yasuo Kurimoto & Masayo Takahashi

  5. Department of Technology Development, Kazusa DNA Research Institute, Kisarazu, Japan

    Ryoji Fujiki & Osamu Ohara

Authors
  1. Akiko Maeda
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  2. Akiko Yoshida
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  3. Kanako Kawai
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  4. Yuki Arai
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  5. Ryutaro Akiba
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  6. Akira Inaba
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  7. Seiji Takagi
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  8. Ryoji Fujiki
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  9. Yasuhiko Hirami
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  10. Yasuo Kurimoto
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  11. Osamu Ohara
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  12. Masayo Takahashi
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Corresponding author

Correspondence to Akiko Maeda.

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Conflicts of interest

A. Maeda, None; A. Yoshida, None; K. Kawai, None; Y. Arai, None; R. Akiba, None; A. Inaba, None; S. Takagi, None; R. Fujiki, None; Y. Hirami, None; Y. Kurimoto, None; O. Ohara, None; M. Takahashi, None.

Additional information

Currently Akiko Maeda, Akiko Yoshida, Kanako Kawai, Akira Inaba, Seiji Takagi, Yasuhiko Hirami, Yasuo Kurimoto, and Masayo Takahashi are also affiliated with Kobe City Eye Hospital.

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Maeda, A., Yoshida, A., Kawai, K. et al. Development of a molecular diagnostic test for Retinitis Pigmentosa in the Japanese population. Jpn J Ophthalmol 62, 451–457 (2018). https://doi.org/10.1007/s10384-018-0601-x

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  • DOI: https://doi.org/10.1007/s10384-018-0601-x

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