June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Genetic Heterogeneity Among Patients with Pericentral Retinitis Pigmentosa
Author Affiliations & Notes
  • Jason Comander
    Ocular Genomics Institute, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA
    Berman-Gund Laboratory for the Study of Retinal Degenerations, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA
  • Aliete Langsdorf
    Ocular Genomics Institute, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA
  • Shyana Harper
    Berman-Gund Laboratory for the Study of Retinal Degenerations, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA
  • Carol Weigel-DiFranco
    Berman-Gund Laboratory for the Study of Retinal Degenerations, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA
  • Mark Consugar
    Ocular Genomics Institute, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA
  • Michael Sandberg
    Berman-Gund Laboratory for the Study of Retinal Degenerations, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA
  • Xiaowu Gai
    Center for Biomedical Informatics, Department of Molecular Pharmacology and Therapeutics, Loyola University Chicago Health Sciences Division, Maywood, IL
  • Joseph White
    Ocular Genomics Institute, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA
  • Eliot Berson
    Berman-Gund Laboratory for the Study of Retinal Degenerations, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA
  • Eric Pierce
    Ocular Genomics Institute, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA
    Berman-Gund Laboratory for the Study of Retinal Degenerations, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA
  • Footnotes
    Commercial Relationships Jason Comander, None; Aliete Langsdorf, None; Shyana Harper, None; Carol Weigel-DiFranco, None; Mark Consugar, Agilent Technologies, Inc. (R); Michael Sandberg, None; Xiaowu Gai, None; Joseph White, None; Eliot Berson, None; Eric Pierce, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 1579. doi:
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      Jason Comander, Aliete Langsdorf, Shyana Harper, Carol Weigel-DiFranco, Mark Consugar, Michael Sandberg, Xiaowu Gai, Joseph White, Eliot Berson, Eric Pierce; Genetic Heterogeneity Among Patients with Pericentral Retinitis Pigmentosa. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1579.

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

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Abstract

Purpose: Pericentral retinitis pigmentosa (RP) is an atypical form of RP that affects the near-peripheral retina first and tends to spare the far periphery (Sandberg et al, AJO, 2005). Mutations in the TOPORS gene have been described in selected pericentral RP families (e.g. Selmer et al, Acta Ophthalmol, 2010). This study was performed to further define the overall mutation spectrum in patients with this phenotype. It remains to be determined to what extent pericentral RP could have similar genetic causes as typical RP, or whether the different phenotype of pericentral RP is a reflection of mutations in novel genes or pathways.

Methods: We identified a cohort of 34 patients from separate families with pericentral RP based on a comprehensive analysis of their retinal phenotype. DNA samples were collected from these patients, along with 14 samples from affected and unaffected relatives. A multistage gene discovery approach was used, starting with selective exon capture and next generation sequencing (NGS) to sequence 196 genes previously associated with inherited retinal degenerations. Then the samples without mutations in known genes underwent analyses of copy number variation (CNV) for deletion detection, followed by whole exome sequencing for novel gene discovery.

Results: The selective exon capture/NGS approach provided a mean depth of coverage of the targeted sequences of >124 fold, and >97% of the targeted sequences were covered with ≥10x depth. Mutations provisionally responsible for disease were found in 5 of the first 12 patients analyzed. These include mutations in RHO (4 patients) and PDE6B (1 patient). No mutations were found in TOPORS. Two mutations have been previously identified in patients with more common forms of typical RP and four mutations appeared to be novel. Sequencing analyses in the remainder of the samples is ongoing.

Conclusions: Initial results suggest that some patients with pericentral RP have mutations in the same genes that cause more common forms of typical RP. Further molecular genetic subtyping of the entire cohort, including ongoing whole exome sequencing, will better define the genetic heterogeneity that appears to exist within this clinical phenotype.

Keywords: 696 retinal degenerations: hereditary • 695 retinal degenerations: cell biology • 539 genetics  
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