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.