Skip to main content
SpringerLink
Log in

Long-term clinical course of 2 Japanese patients with PRPF31-related retinitis pigmentosa

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

Abstract

Purpose

To assess the long-term clinical course of 2 patients with PRPF31-related retinitis pigmentosa (RP).

Patients and methods

We clinically examined 2 unrelated patients with RP and collected peripheral blood samples from them. Ophthalmic examinations, including best-corrected visual acuity measurements, Goldmann perimetry, full-field electroretinography, fundus autofluorescence imaging, and optical coherence tomography, were also performed. The visual acuity and visual field were continuously monitored. To identify the causative mutations, 74 genes known to cause RP or Leber congenital amaurosis were examined via targeted next-generation sequencing.

Results

The clinical courses of both patients were similar. The onset of nyctalopia occurred in the first decade. Fundus examination showed typical RP. Although the patients’ visual acuity was relatively preserved even into the fourth decade, the visual field area exhibited rapid deterioration in the mid-teens, with severe concentric constriction in the third decade. Mutation analysis revealed PRPF31 mutations as the cause for autosomal dominant RP in both patients.

Conclusions

To the best of our knowledge, few reports of long-term observations pertaining to patients with PRPF31-related RP have been published. The findings reported herein, especially those relating to the progressive degeneration of the visual field, may ultimately play a role in the provision of high-quality counseling for patients with this condition.

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

Similar content being viewed by others

References

  1. Chizzolini M, Galan A, Milan E, Sebastiani A, Costagliola C, Parmeggiani F. Good epidemiologic practice in retinitis pigmentosa: from phenotyping to biobanking. Curr Genom. 2011;12:260–6.

    Article  CAS  Google Scholar 

  2. Hotta Y, Shiono T, Hayakawa M, Hashimoto T, Kanai A, Nakajima A, et al. Molecular biological study of the rhodopsin gene in Japanese patients with autosomal dominant retinitis pigmentosa (in Japanese). Nippon Ganka Gakkai Zasshi. 1992;96:237–42.

    CAS  PubMed  Google Scholar 

  3. Oishi M, Oishi A, Gotoh N, Ogino K, Higasa K, Iida K, et al. Comprehensive molecular diagnosis of a large cohort of Japanese retinitis pigmentosa and Usher syndrome patients by next-generation sequencing. Invest Ophthalmol Vis Sci. 2014;55:7369–75.

    Article  CAS  PubMed  Google Scholar 

  4. Makarov EM, Makarova OV, Urlaub H, Gentzel M, Will CL, Wilm M, et al. Small nuclear ribonucleoprotein remodeling during catalytic activation of the spliceosome. Science. 2002;298:2205–8.

    Article  CAS  PubMed  Google Scholar 

  5. Sato H, Wada Y, Itabashi T, Nakamura M, Kawamura M, Tamai M. Mutations in the pre-mRNA splicing gene, PRPF31, in Japanese families with autosomal dominant retinitis pigmentosa. Am J Ophthalmol. 2005;140:537–40.

    Article  CAS  PubMed  Google Scholar 

  6. Audo I, Bujakowska K, Mohand-Saïd S, Lancelot ME, Moskova-Doumanova V, Waseem NH, et al. Prevalence and novelty of PRPF31 mutations in French autosomal dominant rod-cone dystrophy patients and a review of published reports. BMC Med Genet. 2010;11:145. https://doi.org/10.1186/1471-2350-11-145.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Yang Y, Tian D, Lee J, Zeng J, Zhang H, Chen S, et al. Clinical and genetic identification of a large Chinese family with autosomal dominant retinitis pigmentosa. Ophthalmic Genet. 2015;36:64–9.

    Article  PubMed  Google Scholar 

  8. Xu F, Sui R, Liang X, Li H, Jiang R, Dong F. Novel PRPF31 mutations associated with Chinese autosomal dominant retinitis pigmentosa patients. Mol Vis. 2012;18:3021–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Ogino K, Oishi A, Oishi M, Gotoh N, Morooka S, Sugahara M, et al. Efficacy of column scatter plots for presenting retinitis pigmentosa phenotypes in a Japanese cohort. Transl Vis Sci Technol. 2016. https://doi.org/10.1167/tvst.5.2.4.

    PubMed  PubMed Central  Google Scholar 

  10. Abu-Safieh L, Vithana EN, Mantel I, Holder GE, Pelosini L, Bird AC, et al. A large deletion in the adRP gene PRPF31: evidence that haploinsufficiency is the cause of disease. Mol Vis. 2006;12:384–8.

    CAS  PubMed  Google Scholar 

  11. Marmor MF, Fulton AB, Holder GE, Miyake Y, Brigell M, Bach M. ISCEV standard for full-field clinical electroretinography (2008 update). Doc Ophthalmol. 2009;118:69–77.

    Article  CAS  PubMed  Google Scholar 

  12. National Institutes of Health. ImageJ. http://rsbweb.nih.gov/ij/. Accessed 6 May 2017.

  13. Hosono K, Harada Y, Kurata K, Hikoya A, Sato M, Minoshima S, et al. Novel GUCY2D gene mutations in Japanese male twins with Leber congenital amaurosis. J Ophthalmol. 2015. https://doi.org/10.1155/2015/693468.

    PubMed  PubMed Central  Google Scholar 

  14. Daiger SD, Sullivan LS, Bowne SJ. The retinal information network. The University of Texas Health Science Center, USA. http://www.sph.uth.tmc.edu/Retnet/. Accessed 23 Jan 2014.

  15. The 1000 Genomes Project data. In: The 1000 genomes project consortium. http://www.1000genomes.org/. Accessed 6 May 2017.

  16. ExAC database. In: The Exome aggregation consortium. http://exac.broadinstitute.org/. Accessed 6 May 2017.

  17. Higasa K, Miyake N, Yoshimura J. Human genetic variation database. Kyoto University, Japan. http://www.genome.med.kyoto-u.ac.jp/SnpDB/. Accessed 6 May 2017.

  18. Integrative Japanese Genome Variation Database. Tohoku University, Japan. https://ijgvd.megabank.tohoku.ac.jp/. Accessed 6 May 2017.

  19. The Human Gene Mutation Database. Institute of Medical Genetics in Cardiff. http://www.hgmd.cf.ac.uk/ac/index.php. Accessed 6 May 2017.

  20. Hosono K, Ishigami C, Takahashi M, Park DH, Hirami Y, Nakanishi H, et al. Two novel mutations in the EYS gene are possible major causes of autosomal recessive retinitis pigmentosa in the Japanese population. PLoS One. 2012. https://doi.org/10.1371/journal.pone.0031036.e31036.

    Google Scholar 

  21. Sullivan LS, Bowne SJ, Reeves MJ, Blain D, Goetz K, Ndifor V, et al. Prevalence of mutations in eyeGENE probands with a diagnosis of autosomal dominant retinitis pigmentosa. Invest Ophthalmol Vis Sci. 2013;54:6255–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Rio Frio T, Wade NM, Ransijn A, Berson EL, Beckmann JS, Rivolta C. Premature termination codons in PRPF31 cause retinitis pigmentosa via haploinsufficiency due to nonsense-mediated mRNA decay. J Clin Invest. 2008;118:1519–31.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Hartong DT, Berson EL, Dryja TP. Retinitis pigmentosa. Lancet. 2006;368:1795–809.

    Article  CAS  PubMed  Google Scholar 

  24. Van Cauwenbergh C, Coppieters F, Roels D, De Jaegere S, Flipts H, De Zaeytijd J, et al. Mutations in splicing factor genes are a major cause of autosomal dominant retinitis pigmentosa in Belgian families. PLoS One. 2017;12:e0170038.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Coussa RG, Chakarova C, Ajlan R, Taha M, Kavalec C, Gomolin J, et al. Genotype and phenotype studies in autosomal dominant retinitis pigmentosa (adRP) of the French Canadian founder population. Invest Ophthalmol Vis Sci. 2015;56:8297–305.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Sullivan LS, Bowne SJ, Birch DG, Hughbanks-Wheaton D, Heckenlively JR, Lewis RA, et al. Prevalence of disease-causing mutations in families with autosomal dominant retinitis pigmentosa: a screen of known genes in 200 families. Invest Ophthalmol Vis Sci. 2006;47:3052–64.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Waseem NH, Vaclavik V, Webster A, Jenkins SA, Bird AC, Bhattacharya SS. Mutations in the gene coding for the pre-mRNA splicing factor, PRPF31, in patients with autosomal dominant retinitis pigmentosa. Invest Ophthalmol Vis Sci. 2007;48:1330–4.

    Article  PubMed  Google Scholar 

  28. Gandra M, Anandula V, Authiappan V, Sundaramurthy S, Raman R, Bhattacharya S, et al. Retinitis pigmentosa: mutation analysis of RHO, PRPF31, RP1, and IMPDH1 genes in patients from India. Mol Vis. 2008;14:1105–13.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Vithana EN, Abu-Safieh L, Pelosini L, Winchester E, Hornan D, Bird AC, et al. Expression of PRPF31 mRNA in patients with autosomal dominant retinitis pigmentosa: a molecular clue for incomplete penetrance? Invest Ophthalmol Vis Sci. 2003;44:4204–9.

    Article  PubMed  Google Scholar 

  30. Suto K, Hosono K, Takahashi M, Hirami Y, Arai Y, Nagase Y, et al. Clinical phenotype in ten unrelated Japanese patients with mutations in the EYS gene. Ophthalmic Genet. 2014;35:25–34.

    Article  CAS  PubMed  Google Scholar 

  31. Hafler BP, Comander J, Weigel DiFranco C, Place EM, Pierce EA. Course of ocular function in PRPF31 retinitis pigmentosa. Semin Ophthalmol. 2016;31:49–52.

    Article  PubMed  Google Scholar 

  32. Al-Maghtheh M, Vithana E, Tarttelin E, Jay M, Evans K, Moore T, et al. Evidence for a major retinitis pigmentosa locus on 19q13.4 (RP11) and association with a unique bimodal expressivity phenotype. Am J Hum Genet. 1996;59:864–71.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Zhong Z, Yan M, Sun W, Wu Z, Han L, Zhou Z, et al. Two novel mutations in PRPF3 causing autosomal dominant retinitis pigmentosa. Sci Rep. 2016;6:37840. https://doi.org/10.1038/srep37840.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Chen X, Liu Y, Sheng X, Tam PO, Zhao K, Chen X. PRPF4 mutations cause autosomal dominant retinitis pigmentosa. Hum Mol Genet. 2014;23:2926–39.

    Article  CAS  PubMed  Google Scholar 

  35. Tanackovic G, Ransijn A, Ayuso C, Harper S, Berson EL, Rivolta C. A missense mutation in PRPF6 causes impairment of pre-mRNA splicing and autosomal-dominant retinitis pigmentosa. Am J Hum Genet. 2011;88:643–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Tarttelin EE, Plant C, Weissenbach J, Bird AC, Bhattacharya SS, Inglehearn CF. A new family linked to the RP13 locus for autosomal dominant retinitis pigmentosa on distal 17p. J Med Genet. 1996;33:518–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Tanackovic G, Ransijn A, Thibault P, Abou Elela S, Klinck R, Berson EL, et al. PRPF mutations are associated with generalised defects in spliceosome formation and pre-mRNA splicing in patients with retinitis pigmentosa. Hum Mol Genet. 2011;20:2116–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Pan X, Chen X, Liu X, Gao X, Kang X, Xu Q, et al. Mutation analysis of pre-mRNA splicing genes in Chinese families with retinitis pigmentosa. Mol Vis. 2014;20:770–9.

    PubMed  PubMed Central  Google Scholar 

  39. Makarova OV, Makarov EM, Liu S, Vornlocher HP, Lührmann R. Protein 61K, encoded by a gene (PRPF31) linked to autosomal dominant retinitis pigmentosa, is required for U4/U6*U5 tri-snRNP formation and pre-mRNA splicing. EMBO J. 2002;21:1148–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Yuan L, Kawada M, Havlioglu N, Tang H, Wu JY. Mutations in PRPF31 inhibit pre-mRNA splicing of rhodopsin gene and cause apoptosis of retinal cells. J Neurosci. 2005;25:748–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Pang CP, Lam DS. Differential occurrence of mutations causative of eye diseases in the Chinese population. Hum Mutat. 2002;19:189–208.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors would like to thank Editage (https://www.editage.jp/) for English language editing. This work was supported by a grant for Initiative on Rare and Undiagnosed Diseases for Adults (no. 16ek0109151h0002) from the Japan Agency for Medical Research and Development (AMED) and by Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research (C) (no. 26462659 awarded to Y.H. and no. 16K11284 awarded to K.H.).

Author information

Authors and Affiliations

  1. Department of Ophthalmology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu-shi, Higashi-ku, Shizuoka, 431-3192, Japan

    Kentaro Kurata, Katsuhiro Hosono & Yoshihiro Hotta

Authors
  1. Kentaro Kurata
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Katsuhiro Hosono
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yoshihiro Hotta
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yoshihiro Hotta.

Ethics declarations

Conflicts of interest

K. Kurata, None; K. Hosono, None; Y. Hotta, None.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 22 kb)

Supplementary material 2 (PDF 71 kb)

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kurata, K., Hosono, K. & Hotta, Y. Long-term clinical course of 2 Japanese patients with PRPF31-related retinitis pigmentosa. Jpn J Ophthalmol 62, 186–193 (2018). https://doi.org/10.1007/s10384-017-0560-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10384-017-0560-7

Keywords

Search

Navigation