Research output per year
Research output per year
Siddharth Srivastava, Jamie A. Love-Nichols, Kira A. Dies, David H. Ledbetter, Christa L. Martin, Wendy K. Chung, Helen Firth, Thomas Frazier, Robin L. Hansen, Lisa Prock, Han Brunner, Ny Hoang, Stephen W. Scherer, Mustafa Sahin*, David T. Miller, Bibiana Restrepo, Suma Shankar, Erin Rooney Riggs, Pete Constantinou, Anne Reed-Weston
Research output: Contribution to journal › (Systematic) Review article › peer-review
Purpose: For neurodevelopmental disorders (NDDs), etiological evaluation can be a diagnostic odyssey involving numerous genetic tests, underscoring the need to develop a streamlined algorithm maximizing molecular diagnostic yield for this clinical indication. Our objective was to compare the yield of exome sequencing (ES) with that of chromosomal microarray (CMA), the current first-tier test for NDDs.
Methods: We performed a PubMed scoping review and meta-analysis investigating the diagnostic yield of ES for NDDs as the basis of a consensus development conference. We defined NDD as global developmental delay, intellectual disability, and/or autism spectrum disorder. The consensus development conference included input from genetics professionals, pediatric neurologists, and developmental behavioral pediatricians.
Results: After applying strict inclusion/exclusion criteria, we identified 30 articles with data on molecular diagnostic yield in individuals with isolated NDD, or NDD plus associated conditions (such as Rett-like features). Yield of ES was 36% overall, 31% for isolated NDD, and 53% for the NDD plus associated conditions. ES yield for NDDs is markedly greater than previous studies of CMA (15-20%).
Conclusion: Our review demonstrates that ES consistently outperforms CMA for evaluation of unexplained NDDs. We propose a diagnostic algorithm placing ES at the beginning of the evaluation of unexplained NDDs.
Original language | English |
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Pages (from-to) | 2413-2421 |
Number of pages | 9 |
Journal | Genetics in Medicine |
Volume | 21 |
Issue number | 11 |
DOIs | |
Publication status | Published - Nov 2019 |
Research output: Contribution to journal › Erratum / corrigendum / retractions › Academic