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The performance of genome sequencing as a first-tier test for neurodevelopmental disorders
- Source :
- European Journal of Human Genetics, 31, 1, pp. 81-88, European Journal of Human Genetics, 31(1), 81-88. Nature Publishing Group, European Journal of Human Genetics, 31, 81-88
- Publication Year :
- 2023
-
Abstract
- Contains fulltext : 290609.pdf (Publisher’s version ) (Open Access) Genome sequencing (GS) can identify novel diagnoses for patients who remain undiagnosed after routine diagnostic procedures. We tested whether GS is a better first-tier genetic diagnostic test than current standard of care (SOC) by assessing the technical and clinical validity of GS for patients with neurodevelopmental disorders (NDD). We performed both GS and exome sequencing in 150 consecutive NDD patient-parent trios. The primary outcome was diagnostic yield, calculated from disease-causing variants affecting exonic sequence of known NDD genes. GS (30%, n = 45) and SOC (28.7%, n = 43) had similar diagnostic yield. All 43 conclusive diagnoses obtained with SOC testing were also identified by GS. SOC, however, required integration of multiple test results to obtain these diagnoses. GS yielded two more conclusive diagnoses, and four more possible diagnoses than ES-based SOC (35 vs. 31). Interestingly, these six variants detected only by GS were copy number variants (CNVs). Our data demonstrate the technical and clinical validity of GS to serve as routine first-tier genetic test for patients with NDD. Although the additional diagnostic yield from GS is limited, GS comprehensively identified all variants in a single experiment, suggesting that GS constitutes a more efficient genetic diagnostic workflow. 01 januari 2023
- Subjects :
- All institutes and research themes of the Radboud University Medical Center
Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7]
Other Research Radboud Institute for Health Sciences [Radboudumc 0]
Genetics
Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6]
Correlated Electron Systems / High Field Magnet Laboratory (HFML)
Genetics (clinical)
Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12]
Subjects
Details
- ISSN :
- 10184813
- Database :
- OpenAIRE
- Journal :
- European Journal of Human Genetics, 31, 1, pp. 81-88, European Journal of Human Genetics, 31(1), 81-88. Nature Publishing Group, European Journal of Human Genetics, 31, 81-88
- Accession number :
- edsair.doi.dedup.....1cbe9ba94a13c894fbcc6b704f44764b