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Semiconductor Sequencing for Preimplantation Genetic Testing for Aneuploidy
Published on: August 25, 2019
Genome sequencing is a sensitive first-line test to diagnose individuals with intellectual disability
Anna Lindstrand1, Marlene Ek1, Malin Kvarnung1
1Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden.
Purpose:
Individuals with intellectual disability (ID) and/or neurodevelopment disorders (NDDs) are currently investigated with several different approaches in clinical genetic diagnostics.
Methods:
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).
Results:
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.
Conclusion:
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.
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