July 2019
Volume 60, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2019
The number of RPGR cases remains under-represented
Author Affiliations & Notes
  • Elise Heon
    Ophthalmology & Vision Sciences, Hospital for Sick Children, Toronto, Ontario, Canada
    Genetics and Genomic Biology, The Hospital for Sick Children, Toronto, Ontario, Canada
  • Anjali Vig
    Genetics and Genomic Biology, The Hospital for Sick Children, Toronto, Ontario, Canada
  • Erika Tavares
    Genetics and Genomic Biology, The Hospital for Sick Children, Toronto, Ontario, Canada
  • Ajoy Vincent
    Ophthalmology & Vision Sciences, Hospital for Sick Children, Toronto, Ontario, Canada
    Genetics and Genomic Biology, The Hospital for Sick Children, Toronto, Ontario, Canada
  • Footnotes
    Commercial Relationships   Elise Heon, Deep Genomics (C), Editas (C); Anjali Vig, None; Erika Tavares, None; Ajoy Vincent, None
  • Footnotes
    Support  The Foundation Fighting Blindness,
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 389. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Elise Heon, Anjali Vig, Erika Tavares, Ajoy Vincent; The number of RPGR cases remains under-represented. Invest. Ophthalmol. Vis. Sci. 2019;60(9):389.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : Identification of the genetic cause of the retinal degeneration in three male patients.

Methods : This study was approved by the ethics board of the Hospital for Sick Children (Toronto). Two male patients affected with retinal degeneration for whom no mutation was identified through standard of care clinical testing, underwent whole genome sequencing (WGS). Another case was studied twice using different CLIA-approved Laboratory. Pedigress were drawn. Clinical information collected related to general health, family and personnal history and ocular phenotyping (VA, exam, imaging, functional studies). DNA was extracted from whole blood using standard procedures. Research based WGS was analysed using internal filtering protocols. Variant validation was done using publicly available tools and segregation analysis. Variant pathogenicity calling respected the criteria of the American College of Medical Geneticists. Final research results were confirmed by a CLIA approved laboratory.

Results : Two of the participants were Caucasian while one was East Indian. RPGR ORF15 were identified, in 3 males who previously a negative genetic testing result, using a different filtering approach of the next generation sequences. Several parameters were changed such as removing the quality pass filter and accepting a lower coverage. The ORF15 variants identified (c.232_2354del and c.2405_2406del) met all our validation parameters and were confirmed by a CLIA approved laboratory. Though there were some phenotype difference between the patients, they all had a visual impairment and an ocular phenotype compatible with an RPGR-related retinal degeneration. Genetic counseling was provided accordingly and the WGS analysis approach for males affected with retinal degeneration was modified.

Conclusions : Because the RPGR sequence is very GC rich, full sequence coverage has been challenging. When doing WGS it has been useful to loosen the traditionally used filtering criteria and accept a lower coverage to identify ORF15 variants. Because gene replacement therapy is being trialed clinically, it is imperative that the real burden of disease be identified.

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.

×