Genome sequencing is a sensitive first-line test to diagnose individuals with intellectual disability.

Lindstrand A, Ek M, Kvarnung M, Anderlid BM, Björck E, Carlsten J, Eisfeldt J, Grigelioniene G, Gustavsson P, Hammarsjö A, Helgadóttir HT, Hellström-Pigg M, Kuchinskaya E, Lagerstedt-Robinson K, Levin LÅ, Lieden A, Lindelöf H, Malmgren H, Nilsson D, Svensson E, Paucar M, Sahlin E, Tesi B, Tham E, Winberg J, Winerdal M, Wincent J, Johansson Soller M, Pettersson M, Nordgren A

Genet Med 24 (11) 2296-2307 [2022-11-00; online 2022-09-06]

Individuals with intellectual disability (ID) and/or neurodevelopment disorders (NDDs) are currently investigated with several different approaches in clinical genetic diagnostics. We compared the results from 3 diagnostic pipelines in patients with ID/NDD: genome sequencing (GS) first (N = 100), GS as a secondary test (N = 129), or chromosomal microarray (CMA) with or without FMR1 analysis (N = 421). The diagnostic yield was 35% (GS-first), 26% (GS as a secondary test), and 11% (CMA/FMR1). Notably, the age of diagnosis was delayed by 1 year when GS was performed as a secondary test and the cost per diagnosed individual was 36% lower with GS first than with CMA/FMR1. Furthermore, 91% of those with a negative result after CMA/FMR1 analysis (338 individuals) have not yet been referred for additional genetic testing and remain undiagnosed. Our findings strongly suggest that genome analysis outperforms other testing strategies and should replace traditional CMA and FMR1 analysis as a first-line genetic test in individuals with ID/NDD. GS is a sensitive, time- and cost-effective method that results in a confirmed molecular diagnosis in 35% of all referred patients.

Clinical Genomics Stockholm [Service]

PubMed 36066546

DOI 10.1016/j.gim.2022.07.022

Crossref 10.1016/j.gim.2022.07.022

pii: S1098-3600(22)00874-7