Molecular diagnostic yield of genome sequencing versus targeted gene panel testing in racially and ethnically diverse pediatric patients
Molecular diagnostic yield of genome sequencing versus targeted gene panel testing in racially and ethnically diverse pediatric patients
Abstract PurposeAdoption of genome sequencing (GS) as a first-line test requires evaluation of its diagnostic yield. We evaluated the GS and targeted gene panel (TGP) testing in diverse pediatric patients (probands) with suspected genetic conditions. MethodsProbands with neurologic, cardiac, or immunologic conditions were offered GS and TGP testing. Diagnostic yield was compared using a fully paired study design. Results645 probands (median age 9 years) underwent genetic testing, and 113 (17.5%) received a molecular diagnosis. Among 642 probands with both GS and TGP testing, GS yielded 106 (16.5%) and TGPs yielded 52 (8.1%) diagnoses (P < .001). Yield was greater for GS vs. TGPs in Hispanic/Latino(a) (17.2% vs. 9.5%, P < .001) and White/European American (19.8% vs. 7.9%, P < .001), but not in Black/African American (11.5% vs. 7.7%, P = .22) population groups by self-report. A higher rate of inconclusive results was seen in the Black/African American (63.8%) vs. White/European American (47.6%; P = .01) population group. Most causal copy number variants (17 of 19) and mosaic variants (6 of 8) were detected only by GS. ConclusionGS may yield up to twice as many diagnoses in pediatric patients compared to TGP testing, but not yet across all population groups.
Abhyankar Avinash、Brown Kaitlyn、Ioele Nicolette、Ramos Michelle A.、Rehman Atteeq U.、Edelmann Lisa、Marathe Priya N.、Sebastin Monisha、Wasserstein Melissa P.、Gelb Bruce D.、Zinberg Randi E.、Horowitz Carol R.、Rodriguez Jessica E.、Okur Volkan、Jobanputra Vaidehi、Thomas-Wilson Amanda、Bonini Katherine E.、Greally John M.、Abul-Husn Noura S.、Diaz George A.、Kenny Eimear E.、Gallagher Katie M.、Guha Saurav、Di Biase Miranda、Odgis Jacqueline A.、Suckiel Sabrina A.、Kelly Nicole R.
Molecular Diagnostics, New York Genome CenterDepartment of Pediatrics, Division of Pediatric Genetic Medicine, Children?ˉs Hospital at Montefiore/Montefiore Medical Center/Albert Einstein College of MedicineDepartment of Pediatrics, Division of Pediatric Genetic Medicine, Children?ˉs Hospital at Montefiore/Montefiore Medical Center/Albert Einstein College of MedicineDepartment of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai||Institute for Health Equity Research, Icahn School of Medicine at Mount SinaiMolecular Diagnostics, New York Genome CenterSema4Institute for Genomic Health, Icahn School of Medicine at Mount SinaiDepartment of Pediatrics, Division of Pediatric Genetic Medicine, Children?ˉs Hospital at Montefiore/Montefiore Medical Center/Albert Einstein College of MedicineDepartment of Pediatrics, Division of Pediatric Genetic Medicine, Children?ˉs Hospital at Montefiore/Montefiore Medical Center/Albert Einstein College of MedicineDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai||Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai||Department of Pediatrics, Icahn School of Medicine at Mount SinaiDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount SinaiDepartment of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai||Institute for Health Equity Research, Icahn School of Medicine at Mount SinaiInstitute for Genomic Health, Icahn School of Medicine at Mount SinaiMolecular Diagnostics, New York Genome CenterMolecular Diagnostics, New York Genome Center||Department of Pathology and Cell Biology, Columbia University Irving Medical CenterMolecular Diagnostics, New York Genome CenterInstitute for Genomic Health, Icahn School of Medicine at Mount SinaiDepartment of Pediatrics, Division of Pediatric Genetic Medicine, Children?ˉs Hospital at Montefiore/Montefiore Medical Center/Albert Einstein College of MedicineInstitute for Genomic Health, Icahn School of Medicine at Mount Sinai||Department of Medicine, Icahn School of Medicine at Mount Sinai||Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount SinaiDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai||Department of Pediatrics, Division of Pediatric Genetic Medicine, Children?ˉs Hospital at Montefiore/Montefiore Medical Center/Albert Einstein College of MedicineInstitute for Genomic Health, Icahn School of Medicine at Mount Sinai||Department of Medicine, Icahn School of Medicine at Mount Sinai||Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount SinaiDepartment of Pediatrics, Division of Pediatric Genetic Medicine, Children?ˉs Hospital at Montefiore/Montefiore Medical Center/Albert Einstein College of MedicineMolecular Diagnostics, New York Genome CenterDepartment of Pediatrics, Division of Pediatric Genetic Medicine, Children?ˉs Hospital at Montefiore/Montefiore Medical Center/Albert Einstein College of MedicineInstitute for Genomic Health, Icahn School of Medicine at Mount SinaiInstitute for Genomic Health, Icahn School of Medicine at Mount Sinai||Department of Medicine, Icahn School of Medicine at Mount SinaiDepartment of Pediatrics, Division of Pediatric Genetic Medicine, Children?ˉs Hospital at Montefiore/Montefiore Medical Center/Albert Einstein College of Medicine
医学研究方法遗传学分子生物学
Abhyankar Avinash,Brown Kaitlyn,Ioele Nicolette,Ramos Michelle A.,Rehman Atteeq U.,Edelmann Lisa,Marathe Priya N.,Sebastin Monisha,Wasserstein Melissa P.,Gelb Bruce D.,Zinberg Randi E.,Horowitz Carol R.,Rodriguez Jessica E.,Okur Volkan,Jobanputra Vaidehi,Thomas-Wilson Amanda,Bonini Katherine E.,Greally John M.,Abul-Husn Noura S.,Diaz George A.,Kenny Eimear E.,Gallagher Katie M.,Guha Saurav,Di Biase Miranda,Odgis Jacqueline A.,Suckiel Sabrina A.,Kelly Nicole R..Molecular diagnostic yield of genome sequencing versus targeted gene panel testing in racially and ethnically diverse pediatric patients[EB/OL].(2025-03-28)[2025-05-24].https://www.medrxiv.org/content/10.1101/2023.03.18.23286992.点此复制
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