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Stephen P Daiger, Sara J Bowne, Lori S Sullivan, Kaylie D Webb-Jones, David G Birch, Cheryl Elizabeth Avery, Feng Wang, Rui Chen, Dianna K H Wheaton; Retinal Targeted-Capture Next Generation Sequencing and CLIA Confirmation in Patients with a Range of Inherited Retinal Degeneration. Invest. Ophthalmol. Vis. Sci. 2016;57(12):No Pagination Specified.
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© ARVO (1962-2015); The Authors (2016-present)
To determine the genetic cause of disease in a panel of clinically characterized retinal degeneration patients from Texas and surrounding states. This collection of genotype known, clinically-characterized patients will be a valuable resource for future clinical trials.
Patients with inherited retinal degeneration underwent complete ophthalmic exams and genetic consultations. Ophthalmic exams generally included best-corrected visual acuity, ISCEV standard ERGs, visual field perimetry, dark adaptometry, and retinal imaging. Genomic DNA from each proband was analyzed for the presence of mutation in 163 retinal disease genes using a targeted-capture next-generation sequencing (NGS) research protocol. Di-deoxy sequencing validation of potential disease-causing variants was performed using CLIA protocols.
Eighty-nine unrelated patients with a variety of retinal degenerations were tested. Forty-seven (53%) had a diagnosis of retinitis pigmentosa (RP), 12 (13%) had Leber congenital amaurosis, 13 (15%) had a form of cone dystrophy, 4 (4%) had Usher’s syndrome, and 13 (15%) had a variety of other rare forms of retinal degeneration. The majority of samples, 63%, were isolate in nature with no reported family history of retinal disease. Retinal targeted-capture NGS identified potentially pathogenic mutations in 65 of the 89 patients tested. Pathogenicity analyses, including variant assessment and di–deoxy sequencing of probands and available family members, confirmed pathogenic or likely pathogenic mutations in 57 patients. Five additional patients were found to have variants of unknown significance in retinal–disease associated genes. Pathogenic mutations were spread among 32 different genes. The observed genotype was compared to the reported diagnosis and ophthalmic characterization for each individual for consistency and in some cases allowed for a more precise clinical diagnosis.
Likely disease-causing mutations were identified in 66% of retinal degeneration patients. These genotype–known patients are now an accessible, well characterized resource for enrollment in gene therapy and other clinical trials. This cohort of 89 patients is a pilot for the “Texas1000”, a project in development that aims to determine the genetic cause of retinal degeneration in 1,000 clinically characterized patients in Texas and nearby states.
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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