Journal of Cardiovascular Development and Disease Article Diagnostic Yield of Whole Exome Sequencing in Pediatric Dilated Cardiomyopathy Pamela A. Clin Genet. Diagnostic Exome Sequencing: Diagnostic Yield, Novel Gene Discovery, Expected and Unexpected Results BACKGROUND Over the last three years, the application of whole exome sequencing in a clinical diagnostic setting (DES) has transformed the diagnosis and … In a sample of patients with undiagnosed, suspected genetic conditions, a certain type of exome sequencing method was associated with a higher molecular diagnostic yield … Diagnostic yield and clinical utility of whole exome sequencing using an automated variant prioritization system, EVIDENCE September 2020 Clinical Genetics 98(6) Using WES read depth data to predict copy number variation (CNV) could extend the diagnostic utility of this previously underutilized data by providing clinically important information such as previously unsuspected deletions or duplications. 1–11, 10.1038/nrcardio.2016.25 (2016). Asian J Androl. Sixty-six patients in the UDN faced insurance coverage barriers to WES at the time of enrollment (67% public payer, 26% private payer). Rep. 2015;17:1–9. Diagnostic yield in ID cohort (n = 95) by subgroup distribution through whole genome low-coverage sequencing and medical exome sequencing. Methods: 15/43 (35%) had a pathogenic variant reported, 19/43 (44%) of patients without a pathogenic or likely pathogenic variant reported at least one VUS in a gene related to the patient’s clinical phenotype, and 9/43 (21%) only had a research variant. NIH Although many genes have been associated to Mendelian diseases, the diagnostic yield of genome sequencing remains limited, varying from 8 to 70%2. Gynecol. Kolokotronis K, Pluta N, Klopocki E, Kunstmann E, Messroghli D, Maack C, Tejman-Yarden S, Arad M, Rost S, Gerull B. J Clin Med. Sawyer SL, Hartley T, Dyment DA et al. 2. Objective:To characterize the diagnostic yield of combined … Violin plots of coverage among 17 “core” genes related to HCM and DCM. Diagnostic yield in these studies, defined as the proportion of tested patients with . 3 pathogenic or likely pathogenic were found among the 26 DCM patients (diagnostic yield 12%). Epub 2018 Oct 15. RESEARCH ARTICLE Increasing the diagnostic yield of exome sequencing by copy number variant analysis Daniel S. Marchuk ID 1, Kristy Crooks2, Natasha Strande ID 1,2, Kathleen Kaiser-Rogers1,2,3, Laura V. Milko1, Alicia Brandt ID 1, Alexandra Arreola2¤, Christian R. Tilley ID 1, Chris Bizon4, Neeta L. Vora5, Kirk C. Wilhelmsen1,4, James P. Evans1, Jonathan S. Berg1* Epub 2016 Dec 21. | In a sample of patients with undiagnosed, suspected genetic conditions, a certain type of exome sequencing method was associated with a higher molecular diagnostic yield … Coverage of commercial gene panels is given as reference. This site needs JavaScript to work properly. main outcome measures: Diagnostic yield and acceptability of whole exome sequencing in patients with retinal disorders. Conclusions: Methods DNA from 330 probands (age range, 0–68 years) with suspected genetic disorders were subjected to WES. & Fonarow, G. C. Epidemiology and aetiology of heart failure. As whole exome sequencing (WES) becomes more widely used in the clinical realm, a wealth of unanalyzed information will be routinely generated. Eur J Hum Genet. Recent years have seen the growing implementation of next-generation sequencing (NGS) techniques into widespread clinical use, revolutionizing the diagnostic odyssey for many families with monogenic disorders (Yang et al., 2013; Stranneheim and Wedell, 2016). The diagnostic yield and resulting clinical actions of WES for patients who previously faced insurance coverage barriers have not yet been explored. In WES, protein-coding regions of all genes (approximately 20,000) of the human genome, known as the exome, are sequenced using next-generation sequencing technologies. Please enable it to take advantage of the complete set of features! In addition, an evaluation of the clinical characteristics that influence the likelihood of identifying a genetic cause and assessed the potential impact of the genetic diagnosis on … Identification patients in the UDN undergoing whole exome sequencing (WES) previously facing insurance…, Figure 2.. Insurance coverage barriers to clinical…. 2021 Jan-Feb;23(1):69-73. doi: 10.4103/aja.aja_36_20. U01 HG007690/HG/NHGRI NIH HHS/United States, U01 HG007708/HG/NHGRI NIH HHS/United States, U01 HG007674/HG/NHGRI NIH HHS/United States, U01 HG007672/HG/NHGRI NIH HHS/United States, U01 HG007703/HG/NHGRI NIH HHS/United States, U01 HG007942/HG/NHGRI NIH HHS/United States, U01 HG007709/HG/NHGRI NIH HHS/United States, U01 HG010218/HG/NHGRI NIH HHS/United States, U01 HG007530/HG/NHGRI NIH HHS/United States, F32 HG000130/HG/NHGRI NIH HHS/United States. The potential diagnostic yield of whole exome sequencing in pregnancies complicated by fetal ultrasound anomalies Publication Publication. This study investigated the diagnostic yield of EVIDENCE in patients suspected genetic disorders. See this image and copyright information in PMC. 51. DNA from 330 probands (age range, 0‐68 years) with suspected genetic disorders were subjected to whole exome sequencing. targeted or whole exome. The MOGE(S) classification for a phenotype-genotype nomenclature of cardiomyopathy: Endorsed by the world heart federation. To evaluate the diagnostic yield of prenatal whole exome sequencing (WES) for monogenic disorders in fetuses with structural malformations and normal results on cytogenetic testing, and to describe information on pathogenic variants that is provided by WES. Timothy Shin … J. As a result, many such patients remain on a diagnostic odyssey. -, Hershberger RE, Hedges DJ, Morales A. Dilated cardiomyopathy: the complexity of a diverse genetic architecture. 2020, Epub ahead of print. Epub 2019 Oct 14. mutations for the rest continue to be discovered, primarily by whole exome sequencing (WES).1,2 In a group of patients suspected to have genetic diseases, the diagnostic rate of WES has been found to range from 30% to 40%, a variation that may be attributed to the numbers and phenotypes of enrolled patients and the anthropologic characteristics of study Background: Despite growing evidence of diagnostic yield and clinical utility of whole exome sequencing (WES) in patients with undiagnosed diseases, there remain significant cost and reimbursement barriers limiting access to such testing. In this study, we performed indirect comparisons of the coverage and diagnostic yield of WES on genes and variants related to HCM and DCM versus 4 different commercial gene panels using 40 HCM and DCM patients, assuming perfect coverage in those panels. 2020 Aug 25;6(4):a005165. Particularly in children with neuromuscular and skeletal dysplasia phenotypes, performing a ‘trio exome’ also contributed to a higher diagnostic yield. BACKGROUND: Despite growing evidence of diagnostic yield and clinical utility of whole exome sequencing (WES) in patients with undiagnosed diseases, there remain significant cost and reimbursement barriers limiting access to such testing. Article; Open Access; Published: 18 July 2018 Coverage and diagnostic yield of Whole Exome Sequencing for the Evaluation of Cases with Dilated and Hypertrophic Cardiomyopathy. COVID-19 is an emerging, rapidly evolving situation. Figure 3.. Snoeijen-Schouwenaars et. Cardiol. Figure 2.. Insurance coverage barriers to clinical WES. Gynecol. In 21/75 patients a disease-causing variant could be identified among them variants in known SRS genes ... WES approaches significantly increase the diagnostic yield … Here, we report the added diagnostic yield achieved for 101 WES cases re-analyzed 1 to 7years after initial analysis. NIH The diagnostic yield of whole-exome sequencing targeting a gene panel for hearing impairment in … View 4 peer reviews of Diagnostic yield and clinical utility of whole exome sequencing using an automated variant prioritization system,EVIDENCE on Publons COVID-19 : add an open review or score for a COVID-19 paper now to ensure the latest research gets the extra scrutiny it needs. We performed a retrospective descriptive analysis of clinical WES outcomes for patients facing insurance coverage barriers prior to clinical WES and who subsequently enrolled in the Undiagnosed Diseases Network (UDN). Background Early-onset scoliosis (EOS), defined by an onset age of scoliosis less than 10 years, conveys significant health risk to affected children. Glob. DCM typically remains clinically silent until adulthood, yet symptomatic disease can develop in childhood. Increasing the diagnostic yield of exome sequencing by copy number variant analysis. Conclusions: WES increases the yield of molecular diagnosis over standard diagnostic testing. Whole Exome Sequencing (WES) is a robust and one of the most comprehensive genetic tests for identifying the disease-causing changes in a large variety of genetic disorders. Figure 1.. -, Arbustini E, et al. 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. 2020, Epub ahead of print. One test for all: whole exome sequencing signicantly improves the diagnostic yield in growth retarded patients referred for molecular testing for Silver–Russell syndrome Robert Meyer1, Matthias Begemann1, Christian Thomas Hübner1, Daniela Dey1, Alma Kuechler2, Cardiomyopathy phenotypes in human-induced pluripotent stem cell-derived cardiomyocytes-a systematic review. National Center for Biotechnology Information, Unable to load your collection due to an error, Unable to load your delegates due to an error, Sixty-six of 165 (40%) patients undergoing WES had no documented insurance coverage for WES prior to the UDN evaluation. WGS – whole genome sequencing; WES – whole exome sequencing; UDN – Undiagnosed Diseases Network. Exome sequencing is currently recommended as a first-tier clinical diagnostic test for individuals with neurodevelopmental disorders. WES was performed on 180 patients with early-onset epilepsy (≤5 years) of unknown cause. Please enable it to take advantage of the complete set of features! | (2019) assessed the diagnostic yield of whole exome sequencing (WES). Targeted next generation sequencing of gene panels has become a popular tool for the genetic diagnosis of hypertrophic (HCM) and dilated cardiomyopathy (DCM). No other authors have relevant conflicts of interest to disclose. 2020 Jul 9;9(7):2168. doi: 10.3390/jcm9072168. | With the implementation of next generation sequencing ... whole exome sequencing (WES), and trio-based WES. Rev. Methods DNA from 330 probands (age range, 0–68 years) with suspected genetic disorders were subjected to WES. RESEARCH ARTICLE Open Access Enhanced diagnostic yield in Meckel-Gruber and Joubert syndrome through exome sequencing supplemented with split-read mapping Christopher M. Watson1,2*, Laura A. Crinnion1,2, Ian R. Berry1, Sally M. Harrison2, Carolina Lascelles2, Agne Antanaviciute2, Ruth S. Charlton1, Angus Dobbie1, Ian M. Carr2 and David T. Bonthron1,2 Cardiol. 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