June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Peripherin-2 mutations identified by whole exome sequencing in clinically heterogeneous families with retinal pattern dystrophies
Author Affiliations & Notes
  • Mercedes B Villalonga
    Ophthalmic Epidemiology and Genetics Service, Tufts Medical Center, Boston, Massachusetts, United States
  • Giliann K Collins
    Ophthalmic Epidemiology and Genetics Service, Tufts Medical Center, Boston, Massachusetts, United States
  • Rachel E Silver
    Ophthalmic Epidemiology and Genetics Service, Tufts Medical Center, Boston, Massachusetts, United States
  • Johanna M Seddon
    Ophthalmic Epidemiology and Genetics Service, Tufts Medical Center, Boston, Massachusetts, United States
    Department of Ophthalmology, Tufts University School of Medicine, Boston, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Mercedes Villalonga, None; Giliann Collins, None; Rachel Silver, None; Johanna Seddon, Apellis (C), Novartis (F)
  • Footnotes
    Support  JMS: R01-EY011309 from the National Institutes of Health; the Massachusetts Lions Eye Research Fund Inc., New Bedford, MA; and the Age-Related Macular Degeneration Research Fund, Ophthalmic Epidemiology and Genetics Service, Tufts Medical Center, Tufts University School of Medicine, Boston, MA.
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 2777. doi:
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    • Get Citation

      Mercedes B Villalonga, Giliann K Collins, Rachel E Silver, Johanna M Seddon; Peripherin-2 mutations identified by whole exome sequencing in clinically heterogeneous families with retinal pattern dystrophies. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2777.

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

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Abstract

Purpose : Pattern dystrophies are retinal diseases following an autosomal dominant mode of inheritance. Although current research suggests the importance of genetics in this group of clinically heterogeneous diseases, specific loci associated with disease risk are not well established. We investigated coding variants in patients affected by macular and retinal degenerations to determine their role in adult onset inherited retinal diseases.

Methods : All participants were previously enrolled in our genetic and epidemiologic studies of macular and retinal degenerations. We performed whole exome sequencing of 693 samples from family members and unrelated cases and controls. Selection was based on a low macular degeneration polygenic risk score (Yu Y et al. Hum Mol Genet 2011; Yu Y et al. Hum Mol Genet 2014). Affected participants had a diagnosis of either advanced macular degeneration or another retinal disease. We conducted segregation analyses on data from families and filtered variants for pathogenicity using stepwise criteria. Data from our previous targeted sequencing studies were examined to identify additional mutation carriers. Sanger sequencing was used to confirm variant segregation within families.

Results : We identified two families and one unrelated, affected individual carrying the splice variant PRPH2 rs281865373 (c.828+3A>T), as well as one family and four unrelated affected individuals carrying the missense variant PRPH2 rs121918563 (L185P). None of the mutation carriers or other family members carried variants in BEST1 or IMPG1/2. Assessment of longitudinal clinical records, optical coherence tomography, autofluorescence, and infrared imaging obtained for carriers of these mutations revealed retinal pigment epithelial disturbances and lipofuscin deposits. These features are characteristic of the different phenotypic manifestations observed in pattern dystrophies.

Conclusions : Our results suggest that detailed clinical assessment paired with comprehensive genetic analysis is integral to understanding the underlying pathophysiology of inherited retinal diseases. Further genetic investigation will facilitate the accurate classification of these complex and heterogeneous phenotypes.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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