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Kaylie Webb, Dianna Wheaton; Evaluation of Genetic Testing Outcomes for a 4-year Interval of Service Provided to Southwest Eye Registry Participants. Invest. Ophthalmol. Vis. Sci. 2013;54(15):3375.
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© ARVO (1962-2015); The Authors (2016-present)
The Southwest Eye Registry (SER), a regional database of patients with inherited eye diseases, is composed of clinical and genetic data. The registry collects blood samples for genetic testing, genotype-phenotype studies and to advance new gene discovery; an overarching goal is to identify the genetic cause of disease for each registry participant. Successful genotyping can differ from expected disease-causing mutation detection rates and said rates vary according to clinical diagnosis (e.g., ~65% of autosomal dominant RP cases [Bowne IOVS, 2011], ~80% of x-linked RP cases [Sharon Am J Hum Genet, 2003], and ~79% of Stargardt cases [Downes Arch Ophthalmol, 2012]). Described herein is a 4-year interval of practice-based genetic testing outcomes.
The total database size is 4,241 affected and at-risk relatives; ~200 new participants are added per year. DNA is prepped onsite and sent for genetic testing at collaborating clinical diagnostic and research labs according to disease diagnosis. The SER attempts to genotype registry participants using resources available even in cases with phenotypic ambiguity. The majority of samples (98%) are submitted under research protocols rather than fee-for-service submission. A 4-year interval (2008 - 2012) of genetic testing services was evaluated to ascertain how many participants received services, how many DNA samples were submitted for testing, and whether a successful genetic testing outcome was achieved.
During the study interval 803 participants were added to the registry. DNA samples from 709 individuals were sent to one of six centers for genotype analysis; mutation results were returned for 53% of the submitted samples. A gene mutation was identified in 81% of achromatopsia, 74% of choroideremia, 65% of x-linked RP, 50% of autosomal dominant RP, 49% of Stargardt disease, and 24% of Lebers congenital amaurosis. Observed mutation detection rates were lower than expected (z>2.15, p<0.025) except for achromatopsia (z>0.322, ns). Factors influencing deviations in rates included: indeterminate phenotype, limited testing options, cost of testing, and genotyping method.
Improved knowledge of genotype-phenotype relationships and advances in mutation detection/gene discovery techniques will improve genetic testing success rates for registry participants.
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