September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Phenotype Based Targeted Next Generation Sequencing Complemented with Microarray Analysis has high yield in Clinical Genetic Testing of Inherited Eye Disorders
Author Affiliations & Notes
  • Suma P Shankar
    Human Genetics , Emory University School of Medicine, Atlanta, Georgia, United States
    Ophthalmology, Emory University School of Medicine, Atlanta, Georgia, United States
  • Jiong Yan
    Ophthalmology, Emory University School of Medicine, Atlanta, Georgia, United States
  • Sarah Richards
    Human Genetics , Emory University School of Medicine, Atlanta, Georgia, United States
  • Brian Bunke
    Human Genetics , Emory University School of Medicine, Atlanta, Georgia, United States
  • Madhuri Hegde
    Human Genetics , Emory University School of Medicine, Atlanta, Georgia, United States
  • John Alexander
    Human Genetics , Emory University School of Medicine, Atlanta, Georgia, United States
  • Footnotes
    Commercial Relationships   Suma Shankar, None; Jiong Yan, None; Sarah Richards, None; Brian Bunke, None; Madhuri Hegde, None; John Alexander, None
  • Footnotes
    Support  NIH Departmental Core Grant EY006360 and Research to Prevent Blindness, Inc, New York, New York
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 3159. doi:
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      Suma P Shankar, Jiong Yan, Sarah Richards, Brian Bunke, Madhuri Hegde, John Alexander; Phenotype Based Targeted Next Generation Sequencing Complemented with Microarray Analysis has high yield in Clinical Genetic Testing of Inherited Eye Disorders. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3159.

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      © 2017 Association for Research in Vision and Ophthalmology.

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Abstract

Purpose : To report clinical utility and novel variants identified by targeted Next generation sequencing (NGS) panels, array comparative genomic hybridization (aCGH) panels and mitochondrial genome testing in inherited eye diseases.

Methods : Eye disease-causing genes were tested in 394 individuals with inherited eye diseases including ocular developmental disorders and retinal
dystrophies presenting to eye clinic by either NGS panels alone, NGS panel and mitochondrial genome testing or NGS panel and aCGH. The controls were normal population data from 1000 exome, dbSNP, genome, CNV data base and internal Emory Genetics Lab controls. Genetic test results were classified as pathogenic, likely pathogenic, Variants of unknown significance (VOUS), likely benign or benign per ACMG guidelines.

Results : We observed variations including missense, nonsense and silent changes, splice site variants, small deletions as well as copy number
variants (CNVs) including deletions and duplications; only pathogenic, likely pathogenic, and Variants of unknown significance (VOUS) were reported. Definitive pathogenic sequence variants were identified in 159/394 (40%) individuals, pathogenic deletions were reported in 18/189 (10%) individuals and 135 individuals (34%) had variants that need additional analysis to determine significance. No pathogenic mitochondrial variants related to eye disorders were found in 100 individuals that had testing

Conclusions : Nextgen sequence analysis alone identified ~30% conclusive pathogenic molecular findings and when complemented with aCGH identified an additional 10% contributory disease-causing variation but none from the mitochondrial genome sequence analysis. The most
efficient and cost effective testing is a clinical phenotype driven targeted NGS panel with reflex to aCGH in those that have negative sequencing results. It is not required to include complete mitochondrial genome sequencing in next generation targeted eye panels.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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