Efficacy and economics of targeted panel versus whole-exome sequencing in 878 patients with suspected primary immunodeficiency - 04/02/21
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for the
International Consortium for Immunodeficiencies
Abstract |
Background |
Next-generation sequencing has become a first-line tool for the diagnosis of primary immunodeficiency. However, patient access remains limited because of restricted insurance coverage and a lack of guidelines addressing the use of targeted panels versus whole-exome sequencing (WES).
Objectives |
We sought to compare targeted next-generation sequencing with WES in a global population of patients with primary immunodeficiency.
Methods |
This was a longitudinal study of 878 patients with likely primary immunodeficiency sequenced between 2010 and 2020. Most patients (n = 780) were first sequenced using a 264 gene panel. This was followed by WES in selected cases if a candidate gene was not found. A subset of patients (n = 98) were selected for a WES-only pipeline if the history was atypical for genes within the targeted panel.
Results |
Disease-causing variants were identified in 498 of the 878 probands (56%), encompassing 152 distinct monogenic disorders. Sixteen patients had disorders that were novel at the time of sequencing (1.8%). Diagnostic yield in patients sequenced by targeted panel was 56% (433 of 780 patients), with subsequent WES leading to an additional 18 diagnoses (overall diagnostic yield 58%, 451 of 780 patients). The WES-only approach had a diagnostic yield of 45% (45 of 98 patients), reflecting that these cases had less common clinical and laboratory phenotypes. Cost analysis, based on current commercial WES and targeted panel prices, demonstrated savings ranging from $300 to $950 with a WES-only approach, depending on diagnostic yield.
Conclusions |
Advantages of WES over targeted next-generation sequencing include simplified workflow, reduced overall cost, and the potential for identification of novel diseases.
Il testo completo di questo articolo è disponibile in PDF.Key words : Next-generation sequencing, targeted panel, whole-exome sequencing, primary immunodeficiency, genomics
Abbreviations used : NGS, PID, WES
Mappa
This study was supported by National Institutes of Health (NIH) grant number 1K08AI116979-01 (J.C.), Eleanor and Miles Shore 50th Anniversary Fellowship Award (C.D.P.), NIH grant number 1R01AI139633-01 (R.S.G.), the Samara Turkel Foundation (R.S.G.), and the Perkin Fund (R.S.G.). |
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Disclosure of potential conflict of interest: The spouse of C. D. Platt analyzes next-generation sequencing for Quest Diagnostics. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 147 - N° 2
P. 723-726 - Febbraio 2021 Ritorno al numeroBenvenuto su EM|consulte, il riferimento dei professionisti della salute.
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