Molecular diagnostic yield of genome sequencing versus targeted gene panel testing in racially and ethnically diverse pediatric patients

被引：18

作者：

Abul-Husn, Noura S. ^{[1
,2
,3
,4
]}

Marathe, Priya N. ^{[1
]}

Kelly, Nicole R. ^{[5
]}

Bonini, Katherine E. ^{[1
]}

Sebastin, Monisha

Odgis, Jacqueline A.

Abhyankar, Avinash

Brown, Kaitlyn ^{[7
]}

Di Biase, Miranda ^{[5
]}

Gallagher, Katie M. ^{[5
,8
]}

Guha, Saurav ^{[6
]}

Ioele, Nicolette ^{[5
,9
]}

Okur, Volkan ^{[6
]}

Ramos, Michelle A. ^{[10
,11
]}

Rodriguez, Jessica E. ^{[1
]}

Rehman, Atteeq U. ^{[6
]}

Thomas-Wilson, Amanda ^{[6
]}

Edelmann, Lisa ^{[12
]}

Zinberg, Randi E. ^{[3
]}

Diaz, George A. ^{[3
,5
,13
]}

Greally, John M. ^{[5
]}

Jobanputra, Vaidehi ^{[6
,14
,15
]}

Suckiel, Sabrina A. ^{[1
,2
]}

Horowitz, Carol R. ^{[10
,11
]}

Wasserstein, Melissa P. ^{[5
]}

Kenny, Eimear E. ^{[1
,2
,3
,17
]}

Gelh, Bruce D. ^{[3
,15
,16
,18
]}

机构：

[1] Icahn Sch Med Mt Sinai, Inst Genom Hlth, New York, NY USA

[2] Icahn Sch Med Mt Sinai, Dept Med, New York, NY USA

[3] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY USA

[4] 23andMe Inc, Sunnyvale, CA USA

[5] Childrens Hosp Montefiore, Montefiore Med Ctr, Albert Einstein Coll Med, Dept Pediat,Div Pediat Genet Med, Bronx, NY USA

[6] New York Genome Ctr, Mol Diagnost, New York, NY USA

[7] Ilumina Inc, San Diego, CA USA

[8] Invitae Corp, San Francisco, CA USA

[9] Mem Sloan Kettering Canc Ctr, New York, NY USA

[10] Icahn Sch Med Mt Sinai, Dept Populat Hlth Sci & Policy, New York, NY USA

[11] Icahn Sch Med Mt Sinai, Inst Hlth Equ Res, New York, NY USA

[12] Sema4, Stamford, CT USA

[13] iECURE Inc, Philadelphia, PA USA

[14] Columbia Univ, Dept Pathol & Cell Biol, Irving Med Ctr, New York, NY USA

[15] Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY USA

[16] Icahn Sch Med Mt Sinai, Dept Pediat, New York, NY USA

[17] Icahn Sch Med Mt Sinai, One Gustave L Levy Pl,Box 1041, New York, NY 10029 USA

[18] Icahn Sch Med Mt Sinai, One Gustave L Levy Pl,Box 1040, New York, NY 10029 USA

来源：

GENETICS IN MEDICINE | 2023年 / 25卷 / 09期

基金：

美国国家卫生研究院;

关键词：

Clinical genetics; Genetic testing; Genomic medicine; Genomics; Molecular diagnostic test; JOINT CONSENSUS RECOMMENDATION; MEDICAL GENETICS; AMERICAN-COLLEGE; CLINICAL UTILITY; EXOME; STANDARDS; GUIDELINES; VARIANTS; CHILDREN; ACMG;

D O I：

10.1016/j.gim.2023.100880

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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: A total of 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 (P < .001). Yield was greater for GS vs TGPs in Hispanic/Latino(a) (17.2% vs 9.5%, P < .001) and White/European American (19.8% vs 7.9%, P < .001) but not in Black/African American (11.5% vs 7.7%, P = .22) population groups by self-report. A higher rate of inconclusive results was seen in the Black/African American (63.8%) vs White/European American (47.6%; P = .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 with TGP testing but not yet across all population groups. & COPY; 2023 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.

引用

页数：11

共 39 条

[1] Diagnostic yield of next-generation sequencing in 87 families with neurodevelopmental disorders [J].

Alvarez-Mora, Maria Isabel ;

Sanchez, Aurora ;

Rodriguez-Revenga, Laia ;

Corominas, Jordi ;

Rabionet, Raquel ;

Puig, Susana ;

Madrigal, Irene .

ORPHANET JOURNAL OF RARE DISEASES, 2022, 17 (01)

[2]

AmbryGenetics, US

[3] The Clinical Sequencing Evidence-Generating Research Consortium: Integrating Genomic Sequencing in Diverse and Medically Underserved Populations [J].

Amendola, Laura M. ;

Berg, Jonathan S. ;

Horowitz, Carol R. ;

Angelo, Frank ;

Bensen, Jeannette T. ;

Biesecker, Barbara B. ;

Biesecker, Leslie G. ;

Cooper, Gregory M. ;

East, Kelly ;

Filipski, Kelly ;

Fullerton, Stephanie M. ;

Gelb, Bruce D. ;

Goddard, Katrina A. B. ;

Hailu, Benyam ;

Hart, Ragan ;

Hassmiller-Lich, Kristen ;

Joseph, Galen ;

Kenny, Eimear E. ;

Koenig, Barbara A. ;

Knight, Sara ;

Kwok, Pui-Yan ;

Lewis, Katie L. ;

McGuire, Amy L. ;

Norton, Mary E. ;

Ou, Jeffrey ;

Parsons, Donald W. ;

Powell, Bradford C. ;

Risch, Neil ;

Robinson, Mimsie ;

Rini, Christine ;

Scollon, Sarah ;

Slavotinek, Anne M. ;

Veenstra, David L. ;

Wasserstein, Melissa P. ;

Wilfond, Benjamin S. ;

Hindorff, Lucia A. ;

Plon, Sharon E. ;

Jarvik, Gail P. .

AMERICAN JOURNAL OF HUMAN GENETICS, 2018, 103 (03) :319-327

[4]

[Anonymous], CONSTITUTIONAL WHOLE

[5]

[Anonymous], MORE COMPLETE STORY

[6] Best practices for the interpretation and reporting of clinical whole genome sequencing [J].

Austin-Tse, Christina A. ;

Jobanputra, Vaidehi ;

Perry, Denise L. ;

Bick, David ;

Taft, Ryan J. ;

Venner, Eric ;

Gibbs, Richard A. ;

Young, Ted ;

Barnett, Sarah ;

Belmont, John W. ;

Boczek, Nicole ;

Chowdhury, Shimul ;

Ellsworth, Katarzyna A. ;

Guha, Saurav ;

Kulkarni, Shashikant ;

Marcou, Cherisse ;

Meng, Linyan ;

Murdock, David R. ;

Rehman, Atteeq U. ;

Spiteri, Elizabeth ;

Thomas-Wilson, Amanda ;

Kearney, Hutton M. ;

Rehm, Heidi L. .

NPJ GENOMIC MEDICINE, 2022, 7 (01)

[7] The question of WGS's clinical utility remains unanswered [J].

Battke, Florian ;

Schulte, Bjorn ;

Schulze, Martin ;

Biskup, Saskia .

EUROPEAN JOURNAL OF HUMAN GENETICS, 2021, 29 (05) :722-723

[8] Whole-genome sequencing is more powerful than whole-exome sequencing for detecting exome variants [J].

Belkadi, Aziz ;

Bolze, Alexandre ;

Itan, Yuval ;

Cobat, Aurelie ;

Vincent, Quentin B. ;

Antipenko, Alexander ;

Shang, Lei ;

Boisson, Bertrand ;

Casanova, Jean-Laurent ;

Abel, Laurent .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2015, 112 (17) :5473-5478

[9]

Bick D, 2017, J PEDIATR GENET, V6, P61, DOI 10.1055/s-0036-1593968

[10]

Biesecker LG, 2014, NEW ENGL J MED, V370, P2418, DOI [10.1056/NEJMra1312543, 10.1056/NEJMc1408914]

← 1 2 3 4 →