种族和民族多样化的儿科患者中全基因组测序与靶向基因panel检测的分子诊断率
Molecular diagnostic yield of genome sequencing versus targeted gene panel testing in racially and ethnically diverse pediatric patients.
作者信息
Abul-Husn Noura S, Marathe Priya N, Kelly Nicole R, Bonini Katherine E, Sebastin Monisha, Odgis Jacqueline A, Abhyankar Avinash, Brown Kaitlyn, Di Biase Miranda, Gallagher Katie M, Guha Saurav, Ioele Nicolette, Okur Volkan, Ramos Michelle A, Rodriguez Jessica E, Rehman Atteeq U, Thomas-Wilson Amanda, Edelmann Lisa, Zinberg Randi E, Diaz George A, Greally John M, Jobanputra Vaidehi, Suckiel Sabrina A, Horowitz Carol R, Wasserstein Melissa P, Kenny Eimear E, Gelb Bruce D
机构信息
Institute for Genomic Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
出版信息
medRxiv. 2023 Mar 20:2023.03.18.23286992. doi: 10.1101/2023.03.18.23286992.
PURPOSE
Adoption of genome sequencing (GS) as a first-line test requires evaluation of its diagnostic yield. We evaluated the GS and targeted gene panel (TGP) testing in diverse pediatric patients (probands) with suspected genetic conditions.
METHODS
Probands with neurologic, cardiac, or immunologic conditions were offered GS and TGP testing. Diagnostic yield was compared using a fully paired study design.
RESULTS
645 probands (median age 9 years) underwent genetic testing, and 113 (17.5%) received a molecular diagnosis. Among 642 probands with both GS and TGP testing, GS yielded 106 (16.5%) and TGPs yielded 52 (8.1%) diagnoses ( < .001). Yield was greater for GS . TGPs in Hispanic/Latino(a) (17.2% . 9.5%, < .001) and White/European American (19.8% . 7.9%, < .001), but not in Black/African American (11.5% . 7.7%, = .22) population groups by self-report. A higher rate of inconclusive results was seen in the Black/African American (63.8%) . White/European American (47.6%; = .01) population group. Most causal copy number variants (17 of 19) and mosaic variants (6 of 8) were detected only by GS.
CONCLUSION
GS may yield up to twice as many diagnoses in pediatric patients compared to TGP testing, but not yet across all population groups.
目的
采用基因组测序（GS）作为一线检测方法需要评估其诊断率。我们评估了GS和靶向基因panel（TGP）检测在患有疑似遗传疾病的不同儿科患者（先证者）中的应用。
方法
为患有神经、心脏或免疫疾病的先证者提供GS和TGP检测。使用完全配对研究设计比较诊断率。
结果
645名先证者（中位年龄9岁）接受了基因检测，并得到了113例（17.5%）分子诊断结果。在同时接受GS和TGP检测的642名先证者中，GS检测出106例（16.5%）诊断结果，TGP检测出52例（8.1%）诊断结果（<0.001）。GS检测的诊断率高于TGP检测。在西班牙裔/拉丁裔（17.2%对9.5%，<0.001）和白人/欧裔美国人（19.8%对7.9%，<0.001）人群中，GS检测的诊断率更高，但在自我报告的黑人/非裔美国人中（差异无统计学意义）（11.5%对7.7%，P = 0.22）。黑人/非裔美国人（63.8%）的不确定结果发生率高于白人/欧裔美国人（47.6%；P = 0.01）人群。大多数致病拷贝数变异（19例中的17例）和嵌合变异（8例中的其中6例）仅通过GS检测到。
结论
与TGP检测相比，GS在儿科患者中的诊断数量可能高达两倍，但并非在所有人群中都是如此。
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