Purpose
To assess the diagnostic yield and the practicality of implementing whole exome
sequencing within a clinical ophthalmology setting.
Design
Evaluation of a diagnostic protocol.
Methods
Setting
Patient participants were enrolled during clinical appointments in a
university based Ophthalmic Genetics clinic.
Patient Population
Twenty-six patients with a variety of presumed hereditary retinal
dystrophies. Intervention: Participants were offered whole exome sequencing in
addition to clinically available sequencing gene panels between July 2012 and January
2013 to determine the molecular etiology of their retinal dystrophy.
Main Outcome Measures
Diagnostic yield and acceptability of whole exome sequencing in patients with
retinal disorders.
Results
Twenty-six of 29 (~90%) eligible patients who were approached opted to
undergo molecular testing. Each participant chose whole exome sequencing in addition to,
or in lieu of, clinically available sequencing gene panels. Time to obtain informed
consent was manageable in the clinical context. Whole exome sequencing successfully
identified known pathogenic mutations or suspected deleterious variants in 57.7% of
participants. Additionally, one participant had 2 autosomal dominant medically
actionable incidental findings (unrelated to retinopathy) that were reported to enable
the participant to take preventive action and reduce risk for future disease.
Conclusions
In this study, we identified the molecular etiology for more than half of all
participants. Additionally, we found that participants were widely accepting of whole
exome sequencing and the possibility of being informed about medically actionable
incidental findings.