April 2009
Volume 50, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2009
Prognosis for PRPF-RP and Correlation of Phenotype Severity Between Humans and Yeast With the Same Mutations, Suggesting a Common Mechanism
C. F. Inglehearn; K. V. Towns; A. Kipioti; V. Long; M. McKibbin; R. Ramesar; D. A. Mackey; A. T. Moore; E. A. Pierce; J. D. Beggs
Author Affiliations & Notes
  • C. F. Inglehearn
    Leeds Institute of Molecular Medicine, University of Leeds, Leeds, United Kingdom
  • K. V. Towns
    Leeds Institute of Molecular Medicine, University of Leeds, Leeds, United Kingdom
  • A. Kipioti
    Eye Department, St James's University Hospital, Leeds, United Kingdom
  • V. Long
    Eye Department, St James's University Hospital, Leeds, United Kingdom
  • M. McKibbin
    Eye Department, St James's University Hospital, Leeds, United Kingdom
  • R. Ramesar
    Medical School, University of Cape Town, Cape Town, South Africa
  • D. A. Mackey
    Lions Eye Institute, University of Western Australia, Perth, Australia
  • A. T. Moore
    Institute of Ophthalmology, University College London, London, United Kingdom
  • E. A. Pierce
    University of Pennsylvania, Scheie Eye Institute, Philadelphia, Pennsylvania
  • J. D. Beggs
    Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, United Kingdom
  • Footnotes
    Commercial Relationships  C.F. Inglehearn, None; K.V. Towns, None; A. Kipioti, None; V. Long, None; M. McKibbin, None; R. Ramesar, None; D.A. Mackey, None; A.T. Moore, None; E.A. Pierce, None; J.D. Beggs, None.
  • Footnotes
    Support  Wellcome Trust (grant numbers 073477 and 073988)
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 3504. doi:
  • Views
  • Share
  • Tools
    • Alerts
      User Alerts
      You are adding an alert for:
      Prognosis for PRPF-RP and Correlation of Phenotype Severity Between Humans and Yeast With the Same Mutations, Suggesting a Common Mechanism
      You will receive an email whenever this article is corrected, updated, or cited in the literature. You can manage this and all other alerts in My Account
      The alert will be sent to:
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation
      Citation

      C. F. Inglehearn, K. V. Towns, A. Kipioti, V. Long, M. McKibbin, R. Ramesar, D. A. Mackey, A. T. Moore, E. A. Pierce, J. D. Beggs; Prognosis for PRPF-RP and Correlation of Phenotype Severity Between Humans and Yeast With the Same Mutations, Suggesting a Common Mechanism. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3504.

      Download citation file:

      © ARVO (1962-2015); The Authors (2016-present)

      ×
    • Get Permissions
  • Supplements
Abstract

Purpose: : PRPF8-RP is said to be severe but there has been no overview of phenotype across a range of mutations. Haploid yeast carrying seven PRPF8 mutations reveal a temperature-sensitive growth defect that differs in severity between mutations. We therefore collated clinical data from published/new cases to determine an accurate prognosis for PRPF8-RP, establish whether the human phenotype differs between mutations and to see whether such differences parallel those in yeast.

Methods: : Ophthalmic examination was conducted on new patients, a peripheral blood sample was taken, genomic DNA extracted and PRPF8 exons PCR amplified and sequenced.

Results: : We analysed age of onset of disease in PRPF8-RP patients with three different mutations; H2309P, R2310K and H2309R. Average age of onset of nyctalopia for these is 6.6, 22 and 10.7 years respectively. Statistical analysis showed these differences are significant, implying patients carrying H2309P have earliest onset, H2309R begins later and R2310K later still. Analysis of visual acuity in the better eye, plotted against age at examination, again reveals that RP patients with H2309P/H2309R progress more rapidly and have poorer outcomes than R2310K. Interestingly, yeast lines carrying the same mutations have a temperature-sensitive growth defect that varies between mutations, with H2387P and H2387R (equating to human H2309P and H2309R) having a more severe defect than R2388K (equating to human R2310K). The molecular basis of the yeast growth deficit appears to be in the mRNA splicing pathway.

Conclusions: : While effect on peripheral retinal function is severe, PRPF8-RP patients generally retain good visual acuity in at least one eye until the fifth or sixth decade. Patients with H2309P or H2309R have a worse prognosis than those with R2310K, which correlates with observed differences in growth defect severity in yeast lines. The growth defect is attributed to a reduced mRNA splicing activity, and correlation between human and yeast phenotype severity suggests that they may share a common splicing deficit mechanism.

Keywords: clinical (human) or epidemiologic studies: natural history • retinal degenerations: cell biology • proteins encoded by disease genes 
© 2009, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Permission to republish any abstract or part of an abstract in any form must be obtained in writing from the ARVO Office prior to publication.
Copyright © 2024 Association for Research in Vision and Ophthalmology.
×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×
This site uses cookies. By continuing to use our website, you are agreeing to our privacy policy.Accept