Genomic sequencing reanalysis at 12 months boosts mendelian diagnosis and is cost-effectivein intellectual disability

Abstract

Purpose: Whole exome sequencing (WES) has revolutionized Mendelian diagnostics; however, there has not been a consensus on the timing of review of data in undiagnosed individuals and only preliminary data on the cost-effectiveness of this technology. We aimed to assess the utility of WES data reanalysis for diagnosis in Mendelian disorders and to analyze the cost-effectiveness of this technology compared to a traditional diagnostic pathway. Methods: WES was applied to a cohort of 54 patients from 37 families with a variety of Mendelian disorders to identify the genetic basis to their disease. Reanalysis was performed after 12months with an improved WES diagnostic pipeline. A comparison was made between costs of a modeled WES pathway and a traditional diagnostic pathway in a cohort with intellectual disability (ID). Cost-effectiveness of WGS compared to WES was made for a number of hypothetical scenarioswith a range of diagnostic rates and costs ofWGS. Results: Reanalysis of WES data at 12 months following initial assessment improved diagnostic success from 30% to 38% due to interim publication of disease genes, expanded phenotype data from referrer, and an improved bioinformatics pipeline. Cost analysis on the ID cohort showed cost savings when genomic studies were applied early in the patient diagnostic journey. Conclusion: Early application ofWES in Mendelian disorders is cost-effective and reanalysis of undiagnosed individual at a 12-month time point increases diagnoses by 8%.L6200019572018-01-03 <br />