Intellectual Disability Diagnoses Possible With First-Line Genome Sequencing, Study Suggests

For a paper appearing in Genetics in Medicine, a team from the Karolinska Institute, Karolinska University Hospital, and Linköping University evaluates first-line genome sequencing as a tool for diagnosing intellectual disability (ID) and/or neurodevelopmental disorder cases, comparing the approach with diagnostic pipelines that involve secondary genome sequencing or chromosomal microarray-based tests that did or did not include FMR1-focused analyses. Based on data for 100 patients evaluated by first-line genome sequencing, 129 patients tested with secondary genome sequencing, and 421 patients assessed by chromosomal microarrays from 2020 to 2021, the researchers report a higher diagnostic yield, earlier diagnoses, and a reduced cost for the cases in the genome sequencing-first group. "Altogether, our results show that [genome sequencing] as the first-line genetic analysis is feasible and effective, providing a molecular diagnosis for one-third individuals with ID," they write, noting that secondary testing with genome sequencing "captures a similar number of causative variants, this approach is not cost-effective, the time to diagnosis is delayed, and patients are lost to follow up."