Efficacy and economics of targeted panel versus whole-exome sequencing in 878 patients with suspected primary immunodeficiency.
Efficacy and economics of targeted panel versus whole-exome sequencing in 878 patients with suspected primary immunodeficiency.
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878例疑似原发性免疫缺陷患者靶向组与全外显子组测序的疗效和经济学比较
DOI：
10.1016/j.jaci.2020.08.022
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
International Consortium for Immunodeficiencies
中科院分区：
文献类型：
--
作者：
Platt CD;Zaman F;Bainter W;Stafstrom K;Almutairi A;Reigle M;Weeks S;Geha RS;Chou J;International Consortium for Immunodeficiencies
NGS已成为诊断PID的一线工具。然而，由于有限的保险覆盖范围和缺乏针对使用目标小组与WES的指导方针，患者获取仍然有限。在全球原发性免疫缺陷（PID）患者人群中比较靶向下一代测序（NGS）和全外显子组测序（WES）。这是一项在2010年至2020年间对878名可能患有PID测序的患者进行的纵向研究。大多数患者（n=780）首先使用264基因面板进行测序。如果没有找到候选基因，则在选定的病例中进行WES。如果患者的病史与目标组内的基因不典型，则选择一部分患者（n=98）进行WES-only管道。在878个先证者中发现了498个致病变异（56%），包括152种不同的单基因疾病。16例患者在测序时出现了新的疾病（1.8%）。通过靶向小组测序的患者的诊断率为56%（780例患者中有433例），随后的WES导致额外的18例诊断（总诊断率为58%，780例患者中有451例）。仅使用wes方法的诊断率为45%（98例患者中有45例），这反映了这些病例的临床和实验室表型不太常见。基于当前商用WES和目标面板价格的成本分析表明，仅使用WES方法可节省300- 950美元，具体取决于诊断成品率。与靶向NGS相比，WES的优势包括简化工作流程、降低总体成本以及识别新疾病的潜力。878例免疫缺陷先证者的NGS结果表明，WES作为一线诊断检测优于靶向检测，因为它的诊断率更高，成本更低。
NGS has become a first-line tool for diagnosis of PID. However, patient access remains limited due to restricted insurance coverage and a lack of guidelines addressing use of targeted panels vs WES. To compare targeted next generation sequencing (NGS) with whole exome sequencing (WES) in a global population of patients with primary immunodeficiency (PID). This is a longitudinal study of 878 patients with likely PID sequenced between 2010 and 2020. The majority of 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. 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-$950 with a WES-only approach, depending on diagnostic yield. Advantages of WES over targeted NGS include simplified workflow, reduced overall cost, and the potential for identification of novel diseases. NGS of 878 probands with immunodeficiency demonstrates the efficacy of WES as a first-line diagnostic test over targeted panels due to increased diagnostic yield and lower cost.
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影响因子：
9.1
作者：
Tangye, Stuart G.;Al-Herz, Waleed;Sullivan, Kathleen E.
通讯作者：
Sullivan, Kathleen E.
影响因子：
4.4
作者：
Modell, Vicki;Knaus, Megan;Notarangelo, Luigi D.
通讯作者：
Notarangelo, Luigi D.
DOI：
10.1016/j.jaip.2018.12.022
发表时间：
2019-03-01
影响因子：
9.4
作者：
Heimall, Jennifer
通讯作者：
Heimall, Jennifer
影响因子：
7.3
作者：
Mortaz E;Tabarsi P;Mansouri D;Khosravi A;Garssen J;Velayati A;Adcock IM
通讯作者：
Adcock IM
DOI：
10.1038/gim.2015.30
发表时间：
2015-05
期刊：
Genetics in medicine : official journal of the American College of Medical Genetics
影响因子：
--
作者：
Richards S;Aziz N;Bale S;Bick D;Das S;Gastier-Foster J;Grody WW;Hegde M;Lyon E;Spector E;Voelkerding K;Rehm HL;ACMG Laboratory Quality Assurance Committee
通讯作者：
ACMG Laboratory Quality Assurance Committee