Published: 07-09-2022 11:23 | Updated: 07-09-2022 13:43

Genome Sequencing a first-line test to diagnose intellectual disability

DNA Genetic Material Helix
DNA Genetic Material Helix Photo: Gerd Altmann

Researchers at Karolinska Institutet shows in a new study that genome sequencing is a sensitive first-line test to diagnose individuals with intellectual disability. These findings are published in Genetics in Medicine, the official journal of the American College of Medical Genetics and Genomics, ACMG.

Anna Lindstrand
Anna Lindstrand, Adjunct Professor of Clinical Genetics Photo: Stefan Zimmerman.

Individuals with intellectual disability (ID) and/or neurodevelopmental disorders (NDD) are currently investigated with several different approaches in clinical genetic diagnostics. In this study the scientists compared the results from three diagnostic pipelines in patients with ID/NDD; genome-first (n=100), genome as a secondary test (n=129) or chromosomal microarray (CMA) with or without FMR1 analysis (n=421).

The diagnostic yield was 35% (genome-first), 26% (genome as a secondary test) and 11% (CMA/FMR1). Notably, the age of diagnosis was delayed by 1 year when genome was done as a secondary test and the cost per diagnosed individual was 36% lower with genome-first compared to 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 intellectual disability and/or neurodevelopmental disorders”, says Professor Anna Lindstrand at the Department of Molecular Medicine and Surgery, Karolinska Institutet, who led the study. “Genome analysis is a sensitive, time- and cost-effective method that results in a confirmed molecular diagnosis in 35% of all referred patients”, she adds.

The study was supported by the Swedish Research Council, the Stockholm Regional Council, the Strategic Research Area Neuroscience at Ki (StratNeuro), the Swedish Brain Foundation, the Swedish Rare Diseases Research Foundation (Sällsyntafonden). the Hållsten Research Foundation and Sällskapet Barnavård.


Genome sequencing is a sensitive first-line test to diagnose individuals with intellectual disability, Anna Lindstrand, Marlene Ek, Malin Kvarnung, Britt-Marie Anderlid, Erik Björck, Jonas Carlsten, Jesper Eisfeldt, Giedre Grigelioniene, Peter Gustavsson, Anna Hammarsjö, Hafdís T. Helgadóttir, Maritta Hellström-Pigg, Ekaterina Kuchinskaya, Kristina Lagerstedt-Robinson, Lars-Åke Levin, Agne Lieden, Hillevi Lindelöf, Helena Malmgren, Daniel Nilsson, Eva Svensson, Martin Paucar, Ellika Sahlin, Bianca Tesi, Emma Tham, Johanna Winberg, Max Winerdal, Josephine Wincent, Maria Johansson Soller, Maria Pettersson, Ann Nordgren, Genetics in Medicine, online 6 September 2022,