Japanese Journal of Ophthalmology

, Volume 62, Issue 2, pp 186–193 | Cite as

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

  • Kentaro Kurata
  • Katsuhiro Hosono
  • Yoshihiro Hotta
Clinical Investigation
  • 124 Downloads

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.

Keywords

Visual outcome Retinitis pigmentosa PRPF31 Visual field 

Notes

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.).

Conflicts of interest

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

Supplementary material

10384_2017_560_MOESM1_ESM.pdf (22 kb)
Supplementary material 1 (PDF 22 kb)
10384_2017_560_MOESM2_ESM.pdf (72 kb)
Supplementary material 2 (PDF 71 kb)

References

  1. 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.CrossRefGoogle Scholar
  2. 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.PubMedGoogle Scholar
  3. 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.CrossRefPubMedGoogle Scholar
  4. 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.CrossRefPubMedGoogle Scholar
  5. 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.CrossRefPubMedGoogle Scholar
  6. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 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.CrossRefPubMedGoogle Scholar
  8. 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.PubMedPubMedCentralGoogle Scholar
  9. 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.PubMedPubMedCentralGoogle Scholar
  10. 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.PubMedGoogle Scholar
  11. 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.CrossRefPubMedGoogle Scholar
  12. 12.
    National Institutes of Health. ImageJ. http://rsbweb.nih.gov/ij/. Accessed 6 May 2017.
  13. 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.PubMedPubMedCentralGoogle Scholar
  14. 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. 15.
    The 1000 Genomes Project data. In: The 1000 genomes project consortium. http://www.1000genomes.org/. Accessed 6 May 2017.
  16. 16.
    ExAC database. In: The Exome aggregation consortium. http://exac.broadinstitute.org/. Accessed 6 May 2017.
  17. 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. 18.
    Integrative Japanese Genome Variation Database. Tohoku University, Japan. https://ijgvd.megabank.tohoku.ac.jp/. Accessed 6 May 2017.
  19. 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. 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. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Hartong DT, Berson EL, Dryja TP. Retinitis pigmentosa. Lancet. 2006;368:1795–809.CrossRefPubMedGoogle Scholar
  24. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 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.CrossRefPubMedGoogle Scholar
  28. 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.PubMedPubMedCentralGoogle Scholar
  29. 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.CrossRefPubMedGoogle Scholar
  30. 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.CrossRefPubMedGoogle Scholar
  31. 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.CrossRefPubMedGoogle Scholar
  32. 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.PubMedPubMedCentralGoogle Scholar
  33. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 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.CrossRefPubMedGoogle Scholar
  35. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 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.PubMedPubMedCentralGoogle Scholar
  39. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Pang CP, Lam DS. Differential occurrence of mutations causative of eye diseases in the Chinese population. Hum Mutat. 2002;19:189–208.CrossRefPubMedGoogle Scholar

Copyright information

© Japanese Ophthalmological Society 2018

Authors and Affiliations

  • Kentaro Kurata
    • 1
  • Katsuhiro Hosono
    • 1
  • Yoshihiro Hotta
    • 1
  1. 1.Department of OphthalmologyHamamatsu University School of MedicineShizuokaJapan

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