Effectiveness of whole-exome sequencing and costs of the traditional diagnostic trajectory in children with intellectual disability

Abstract

Purpose: This study investigated whole-exome sequencing (WES) yield in a subset of intellectually disabled patients referred to our clinical diagnostic center and calculated the total costs of these patients' diagnostic trajectory in order to evaluate early WES implementation. Methods:We compared 17 patients' trio-WES yield with the retrospective costs of diagnostic procedures by comprehensively examining patient records and collecting resource use information for each patient, beginning with patient admittance and concluding with WES initiation. We calculated cost savings using scenario analyses to evaluate the costs replaced by WES when used as a first diagnostic tool.Results: WES resulted in diagnostically useful outcomes in 29.4% of patients. The entire traditional diagnostic trajectory average cost was $16,409 per patient, substantially higher than the $3,972 trio-WES cost. WES resulted in average cost savings of $3,547 for genetic and metabolic investigations in diagnosed patients and $1,727 for genetic investigations in undiagnosed patients. Conclusion:The increased causal variant detection yield by WES and the relatively high costs of the entire traditional diagnostic trajectory suggest that early implementation of WES is a relevant and costefficient option in patient diagnostics. This information is crucial for centers considering implementation of WES and serves as input for future value-based research into diagnostics. Genet Med advance online publication 4 February 2016

Are whole-exome and whole-genome sequencing approaches cost-effective? A systematic review of the literature

“…3,[31][32][33][34][35][36][37][38][39][40][41][42] Seven studies presented data on the costs of WES or WGS testing pathways, [24][25][26][27][43][44][45] and eight studies presented data on clinically relevant outcome measures for these tests. 5,6,[8][9][10][46][47][48] Of the eight full economic evaluations, two were CUAs 22,23 and six were CEAs, published between 2014 and 2017 in Australia (2), the United States (1), the UK (1), the Netherlands (1), and Canada (1).…”

“…There were no regional differences: the lowest cost estimates in North America (£736; $1,060) 44 and the rest of the world (£382; $555) 32 were similar, but far less with the higher cost estimates (£3,592; $5,169 in North America, 36,38 £3,401; $4,907 in the rest of the world). 40,41 Six studies estimated the cost of WGS, four of which used data from commercial sources. 24,26,28,43 Cost estimates ranged from £1,312 ($1,906) for sequencing using the HiSeq X in Germany 26 to £17,243 ($24,810) for an unspecified platform in Canada.…”

Genetic and phenotypic dissection of 1q43q44 microdeletion syndrome and neurodevelopmental phenotypes associated with mutations in ZBTB18 and HNRNPU

“…Finally, HNRNPU encodes the heterogeneous nuclear ribonucleoprotein (hnRNP) U, an abundant nucleoplasmic phosphoprotein able to bind pre-mRNA in vivo, possibly involved in pre-mRNA splicing (Roshon and Ruley 2005; Ye et al 2015). Eighteen de novo and/or truncating mutations in HNRNPU mutations have been reported in ClinVar, Decipher and in different studies (Carvill et al 2013; de Kovel et al 2016; Epi4K Consortium et al 2013; Hamdan et al 2014; Monroe et al 2016; Need et al 2012; Zhu et al 2015); however, since these mutations were reported each in separate studies and the phenotype of the patients was not described, a specific disorder related to HNRNPU mutations is not yet characterized. Although the description of these patients independently reinforced the previously proposed genotype–phenotype correlations, the dispersion of patients with point mutations in different studies and the absence of comparison with microdeletions did not permit to clearly address the clinical spectra associated with mutations in these genes, nor the possible epistatic or additive genetic interactions.…”

Is the $1000 Genome as Near as We Think? A Cost Analysis of Next-Generation Sequencing

“…These techniques have not only proven to be promising tools in studying the genetics underlying rare Mendelian disorders (12)(13)(14), but have also been shown to be valuable diagnostic tools in genetic diseases (3,8,(15)(16)(17)(18)(19). A recent review showed that although several studies on the cost-effectiveness of NGS applications have been performed, a complete and valid cost overview is currently lacking (20 ).…”