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A Randomized, Controlled Trial of the Analytic and Diagnostic Performance of Singleton and Trio, Rapid Genome and Exome Sequencing in Ill Infants
| Content Provider | Scilit |
|---|---|
| Author | Kingsmore, Stephen F. Cakici, Julie A. Clark, Michelle M. Gaughran, Mary Feddock, Michele Batalov, Sergey Bainbridge, Matthew N. Carroll, Jeanne Caylor, Sara A. Clarke, Christina Ding, Yan Ellsworth, Katarzyna Farnaes, Lauge Hildreth, Amber Hobbs, Charlotte James, Kiely Kint, Cyrielle I. Lenberg, Jerica Nahas, Shareef Prince, Lance Reyes, Iris Salz, Lisa Sanford, Erica Schols, Peter Sweeney, Nathaly Tokita, Mari Veeraraghavan, Narayanan Watkins, Kelly Wigby, Kristen Wong, Terence Chowdhury, Shimul Wright, Meredith S. Dimmock, David Bezares, Zaira Bloss, Cinnamon Braun, Joshua J. A. Diaz, Carlos Mashburn, Dana Tamang, Dorjee Orendain, Daniken Friedman, Jenni Gleeson, Joe Barea, Jaime Chiang, George Cohenmeyer, Casey Coufal, Nicole G. Evans, Marva Honold, Jose Hovey, Raymond L. Kimball, Amy Lane, Brian Le, Crystal Le, Jennie Leibel, Sandra Moyer, Laurel Mulrooney, Patrick Oh, Daeheon Ordonez, Paulina Oriol, Albert Ortiz-Arechiga, Maria Puckett, Laura Speziale, Mark Suttner, Denise Kraan, Lucitia Van Der Knight, Gail Sauer, Charles Song, Richard White, Sarah Wise, Audra Yamada, Catherine |
| Copyright Year | 2019 |
| Description | Journal: American Journal of Human Genetics The second Newborn Sequencing in Genomic Medicine and Public Health study was a randomized, controlled trial of the effectiveness of rapid whole-genome or -exome sequencing (rWGS or rWES, respectively) in seriously ill infants with diseases of unknown etiology. Here we report comparisons of analytic and diagnostic performance. Of 1,248 ill inpatient infants, 578 (46%) had diseases of unknown etiology. 213 infants (37% of those eligible) were enrolled within 96 h of admission. 24 infants (11%) were very ill and received ultra-rapid whole-genome sequencing (urWGS). The remaining infants were randomized, 95 to rWES and 94 to rWGS. The analytic performance of rWGS was superior to rWES, including variants likely to affect protein function, and ClinVar pathogenic/likely pathogenic variants (p < 0.0001). The diagnostic performance of rWGS and rWES were similar (18 diagnoses in 94 infants [19%] versus 19 diagnoses in 95 infants [20%], respectively), as was time to result (median 11.0 versus 11.2 days, respectively). However, the proportion diagnosed by urWGS (11 of 24 [46%]) was higher than rWES/rWGS (p = 0.004) and time to result was less (median 4.6 days, p < 0.0001). The incremental diagnostic yield of reflexing to trio after negative proband analysis was 0.7% (1 of 147). In conclusion, rapid genomic sequencing can be performed as a first-tier diagnostic test in inpatient infants. urWGS had the shortest time to result, which was important in unstable infants, and those in whom a genetic diagnosis was likely to impact immediate management. Further comparison of urWGS and rWES is warranted because genomic technologies and knowledge of variant pathogenicity are evolving rapidly. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6817534/pdf http://www.cell.com/article/S0002929719303131/pdf |
| Ending Page | 733 |
| Page Count | 15 |
| Starting Page | 719 |
| ISSN | 00029297 |
| e-ISSN | 15376605 |
| DOI | 10.1016/j.ajhg.2019.08.009 |
| Journal | American Journal of Human Genetics |
| Issue Number | 4 |
| Volume Number | 105 |
| Language | English |
| Publisher | Elsevier BV |
| Publisher Date | 2019-09-26 |
| Access Restriction | Open |
| Subject Keyword | Journal: American Journal of Human Genetics Intensive Care Unit Whole-genome Sequencing Whole-exome Sequencing Genetic Disease Ultra-rapid Whole-genome Sequencing Genomic Medicine Precision Medicine |
| Content Type | Text |
| Resource Type | Article |
| Subject | Genetics Genetics (clinical) |
