Dataset Information

High Diagnostic Yield of Whole Exome Sequencing in Participants With Retinal Dystrophies in a Clinical Ophthalmology Setting.

ABSTRACT: To assess the diagnostic yield and the practicality of implementing whole exome sequencing within a clinical ophthalmology setting.Evaluation of a diagnostic protocol.setting: Patient participants were enrolled during clinical appointments in a university-based ophthalmic genetics clinic.Twenty-six patients with a variety of presumed hereditary retinal dystrophies.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.Diagnostic yield and acceptability of whole exome sequencing in patients with retinal disorders.Twenty-six of 29 eligible patients (?90%) 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, 1 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.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.

SUBMITTER: Lee K

PROVIDER: S-EPMC4506879 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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High Diagnostic Yield of Whole Exome Sequencing in Participants With Retinal Dystrophies in a Clinical Ophthalmology Setting.

Lee Kristy K Berg Jonathan S JS Milko Laura L Crooks Kristy K Lu Mei M Bizon Chris C Owen Phillips P Wilhelmsen Kirk C KC Weck Karen E KE Evans James P JP Garg Seema S

American journal of ophthalmology 20150422 2

<h4>Purpose</h4>To assess the diagnostic yield and the practicality of implementing whole exome sequencing within a clinical ophthalmology setting.<h4>Design</h4>Evaluation of a diagnostic protocol.<h4>Methods</h4>setting: Patient participants were enrolled during clinical appointments in a university-based ophthalmic genetics clinic.<h4>Patient population</h4>Twenty-six patients with a variety of presumed hereditary retinal dystrophies.<h4>Intervention</h4>Participants were offered whole exome ...[more]

PMID: 25910913

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Project description:Importance:Whole-exome sequencing (WES) has the potential to reveal tumor and germline mutations of clinical relevance, but the diagnostic yield for pediatric patients with solid tumors is unknown. Objective:To characterize the diagnostic yield of combined tumor and germline WES for children with solid tumors. Design:Unselected children with newly diagnosed and previously untreated central nervous system (CNS) and non-CNS solid tumors were prospectively enrolled in the BASIC3 study at a large academic children's hospital during a 23-month period from August 2012 through June 2014. Blood and tumor samples underwent WES in a certified clinical laboratory with genetic results categorized on the basis of perceived clinical relevance and entered in the electronic health record. Main Outcomes and Measures:Clinical categorization of somatic mutations; frequencies of deleterious germline mutations related to patient phenotype and incidental medically-actionable mutations. Results:Of the first 150 participants (80 boys and 70 girls, mean age, 7.4 years), tumor samples adequate for WES were available from 121 patients (81%). Somatic mutations of established clinical utility (category I) were reported in 4 (3%) of 121 patients, with mutations of potential utility (category II) detected in an additional 29 (24%) of 121 patients. CTNNB1 was the gene most frequently mutated, with recurrent mutations in KIT, TSC2, and MAPK pathway genes (BRAF, KRAS, and NRAS) also identified. Mutations in consensus cancer genes (category III) were found in an additional 24 (20%) of 121 tumors. Fewer than half of somatic mutations identified were in genes known to be recurrently mutated in the tumor type tested. Diagnostic germline findings related to patient phenotype were discovered in 15 (10%) of 150 cases: 13 pathogenic or likely pathogenic dominant mutations in adult and pediatric cancer susceptibility genes (including 2 each in TP53, VHL, and BRCA1), 1 recessive liver disorder with hepatocellular carcinoma (TJP2), and 1 renal diagnosis (CLCN5). Incidental findings were reported in 8 (5%) of 150 patients. Most patients harbored germline uncertain variants in cancer genes (98%), pharmacogenetic variants (89%), and recessive carrier mutations (85%). Conclusions and Relevance:Tumor and germline WES revealed mutations in a broad spectrum of genes previously implicated in both adult and pediatric cancers. Combined reporting of tumor and germline WES identified diagnostic and/or potentially actionable findings in nearly 40% of newly diagnosed pediatric patients with solid tumors.

Dataset Information

High Diagnostic Yield of Whole Exome Sequencing in Participants With Retinal Dystrophies in a Clinical Ophthalmology Setting.

Publications

High Diagnostic Yield of Whole Exome Sequencing in Participants With Retinal Dystrophies in a Clinical Ophthalmology Setting.

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