July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Multiple copies of rhodopsin as a novel cause of autosomal dominant retinitis pigmentosa
Author Affiliations & Notes
  • Jacque L Duncan
    Ophthalmology, Univ of California - SF, San Francisco, California, United States
  • Karmen Trzupek
    InformedDNA, St. Petersburg, Florida, United States
  • Joan Fisher
    Foundation Fighting Blindness, Columbia, Maryland, United States
  • Leilla Kenney
    Foundation Fighting Blindness, Columbia, Maryland, United States
  • Sari Tuupanen
    Blueprint Genetics Oy, Biomedicum, Helsinki, Finland
  • Miika Mehine
    Blueprint Genetics Oy, Biomedicum, Helsinki, Finland
  • Stephen P Daiger
    School of Public Health, University of Texas Health Science Center, Houston, Texas, United States
    Ruiz Department of Ophthalmology and Visual Science, University of Texas Health Science Center, Houston, Texas, United States
  • Brian Mansfield
    Foundation Fighting Blindness, Columbia, Maryland, United States
  • Footnotes
    Commercial Relationships   Jacque Duncan, AGTC Therapeutics (C), Editas Medicine (C), Ionis Pharmaceuticals (C), Novelion Therapeutics (C), ProQR Therapeutics (C), SparingVision (C), Spark Therapeutics (C); Karmen Trzupek, AGTC Therapeutics (C), InformedDNA (E), Spark Therapeutics (C); Joan Fisher, None; Leilla Kenney, Foundation Fighting Blindness (E); Sari Tuupanen, Blueprint Genetics (E); Miika Mehine, Blueprint Genetics (E); Stephen Daiger, None; Brian Mansfield, None
  • Footnotes
    Support  Foundation Fighting Blindness
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 2943. doi:
  • Views
  • Share
  • Tools
    • Alerts
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Jacque L Duncan, Karmen Trzupek, Joan Fisher, Leilla Kenney, Sari Tuupanen, Miika Mehine, Stephen P Daiger, Brian Mansfield; Multiple copies of rhodopsin as a novel cause of autosomal dominant retinitis pigmentosa. Invest. Ophthalmol. Vis. Sci. 2019;60(9):2943.

      Download citation file:

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

  • Supplements

Purpose : Advanced genetic testing was conducted in selected individuals with inherited retinal diseases (IRDs) for the purpose of detecting novel disease-causing mechanisms. The selected individuals were part of a large cohort of IRD patients who were initially screened for mutations by targeted-capture next-generation sequencing (NGS).

Methods : The Foundation Fighting Blindness has supported My Retina Tracker®, a registry for IRD patients, since 2016. Registered patients are offered genetic testing which currently consists of screening by Blueprint Genetics (Helsinki, FIN) with a 266-gene retinal dystrophy panel. To date more than 9,900 people have registered with My Retina Tracker and, of these, 3,140 have completed genetic testing. For patients with apparent copy-number variants, additional testing included whole-exome NGS, targeted duplication/deletion analysis, enrollment of other family members, and extended clinical characterization.

Results : Among patients registered with My Retina Tracker and screened by Blueprint Genetics, a 68 year old male with autosomal dominant retinitis pigmentosa (adRP) was found to have multiple copies of the rhodopsin gene, RHO, a common cause of adRP. He had night vision loss, visual field constriction, cystoid macular edema and classical RP. Subsequent testing revealed a complex duplication-rearrangement of chromosome 3q22 which encompasses the entire RHO gene, 5’ regulatory regions and flanking genes. The rearrangement consists of a 48kb triplicated region embedded within a 188kb duplication, resulting in three apparently-intact RHO genes on one chromosome and a fourth, unaltered RHO on the homologous chromosome. No other apparent causes of retinal disease were detected and his unaffected daughter has normal RHO genes, confirming that the rearrangement is on one chromosome only.

Conclusions : The likely cause of adRP in this male is multiple copies of the RHO gene, with perhaps as many as four functional copies. Overexpression of RHO has been demonstrated as the cause of disease in animal models, overexpression is postulated in some human IRD patients, and no other plausible causes were detected. Genes flanking RHO are also affected but are apparently not pathogenic in this case. Overexpression may be a more common cause of RP than expected and may account for a portion of the remaining cases in which mutations have not been detected to date.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.


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.