Meta-analysis and multidisciplinary consensus statement: exome sequencing is a first-tier clinical diagnostic test for individuals with neurodevelopmental disorders
Year: 2019
Type: article
Abstract: 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.
Source: Genetics in Medicine
Institutions: Boston Children's Hospital, Harvard University, Geisinger Medical Center, Autism & Developmental Medicine Institute, Geisinger Health System, Simons Foundation, Columbia University, Cambridge University Hospitals NHS Foundation Trust, Wellcome Sanger Institute, Autism Speaks, University of California Davis Medical Center, University of California, Davis, Radboud University Nijmegen, Maastricht University Medical Centre, Radboud University Medical Center, Maastricht University, Donders Institute for Brain, Cognition and Behaviour, University of Toronto, Hospital for Sick Children, Centre for Applied Genomics
Language: English
Topic: Genomics and Rare Diseases
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,900
Awards: G1044130170, G1470284823, G5827989630
OpenAlex ID: W2953369183