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

Noura S. Abul-Husn; Priya N. Marathe; Nicole R. Kelly; Katherine E. Bonini; Monisha Sebastin; Jacqueline A. Odgis; Avinash Abhyankar; Kaitlyn Brown; Miranda Di Biase; Katie M. Gallagher; Saurav Guha; Nicolette Ioele; Volkan Okur; Michelle A. Ramos; Jessica E. Rodriguez; Atteeq U. Rehman; Amanda Thomas-Wilson; Lisa Edelmann; Randi E. Zinberg; George A. Diaz; John M. Greally; Vaidehi Jobanputra; Sabrina A. Suckiel; Carol R. Horowitz; Melissa P. Wasserstein; Eimear E. Kenny; Bruce D. Gelb

doi:10.1016/j.gim.2023.100880

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

Noura S. Abul-Husn, Priya N. Marathe, Nicole R. Kelly, Katherine E. Bonini, Monisha Sebastin, Jacqueline A. Odgis, Avinash Abhyankar, Kaitlyn Brown, Miranda Di Biase, Katie M. Gallagher, Saurav Guha, Nicolette Ioele, Volkan Okur, Michelle A. Ramos, Jessica E. Rodriguez, Atteeq U. Rehman, Amanda Thomas-Wilson, Lisa Edelmann, Randi E. Zinberg, George A. DiazJohn M. Greally, Vaidehi Jobanputra, Sabrina A. Suckiel, Carol R. Horowitz, Melissa P. Wasserstein, Eimear E. Kenny, Bruce D. Gelb

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

Abstract

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.

Original language	English (US)
Article number	100880
Journal	Genetics in Medicine
Volume	25
Issue number	9
DOIs	https://doi.org/10.1016/j.gim.2023.100880
State	Published - Sep 2023
Externally published	Yes

Keywords

Clinical genetics
Genetic testing
Genomic medicine
Genomics
Molecular diagnostic test

ASJC Scopus subject areas

Genetics(clinical)

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10.1016/j.gim.2023.100880

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Abul-Husn, N. S., Marathe, P. N., Kelly, N. R., Bonini, K. E., Sebastin, M., Odgis, J. A., Abhyankar, A., Brown, K., Di Biase, M., Gallagher, K. M., Guha, S., Ioele, N., Okur, V., Ramos, M. A., Rodriguez, J. E., Rehman, A. U., Thomas-Wilson, A., Edelmann, L., Zinberg, R. E., ... Gelb, B. D. (2023). Molecular diagnostic yield of genome sequencing versus targeted gene panel testing in racially and ethnically diverse pediatric patients. Genetics in Medicine, 25(9), Article 100880. https://doi.org/10.1016/j.gim.2023.100880

Abul-Husn, NS, Marathe, PN, Kelly, NR, Bonini, KE, Sebastin, M, Odgis, JA, Abhyankar, A, Brown, K, Di Biase, M, Gallagher, KM, Guha, S, Ioele, N, Okur, V, Ramos, MA, Rodriguez, JE, Rehman, AU, Thomas-Wilson, A, Edelmann, L, Zinberg, RE, Diaz, GA, Greally, JM, Jobanputra, V, Suckiel, SA, Horowitz, CR, Wasserstein, MP, Kenny, EE & Gelb, BD 2023, 'Molecular diagnostic yield of genome sequencing versus targeted gene panel testing in racially and ethnically diverse pediatric patients', Genetics in Medicine, vol. 25, no. 9, 100880. https://doi.org/10.1016/j.gim.2023.100880

@article{b658810fc2d04295b354a4b7815145c1,

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

abstract = "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.",

keywords = "Clinical genetics, Genetic testing, Genomic medicine, Genomics, Molecular diagnostic test",

author = "Abul-Husn, {Noura S.} and Marathe, {Priya N.} and Kelly, {Nicole R.} and Bonini, {Katherine E.} and Monisha Sebastin and Odgis, {Jacqueline A.} and Avinash Abhyankar and Kaitlyn Brown and {Di Biase}, Miranda and Gallagher, {Katie M.} and Saurav Guha and Nicolette Ioele and Volkan Okur and Ramos, {Michelle A.} and Rodriguez, {Jessica E.} and Rehman, {Atteeq U.} and Amanda Thomas-Wilson and Lisa Edelmann and Zinberg, {Randi E.} and Diaz, {George A.} and Greally, {John M.} and Vaidehi Jobanputra and Suckiel, {Sabrina A.} and Horowitz, {Carol R.} and Wasserstein, {Melissa P.} and Kenny, {Eimear E.} and Gelb, {Bruce D.}",

note = "Publisher Copyright: {\textcopyright} 2023 American College of Medical Genetics and Genomics",

year = "2023",

month = sep,

doi = "10.1016/j.gim.2023.100880",

language = "English (US)",

volume = "25",

journal = "Genetics in Medicine",

issn = "1098-3600",

publisher = "Lippincott Williams and Wilkins",

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TY - JOUR

T1 - Molecular diagnostic yield of genome sequencing versus targeted gene panel testing in racially and ethnically diverse pediatric patients

AU - Abul-Husn, Noura S.

AU - Marathe, Priya N.

AU - Kelly, Nicole R.

AU - Bonini, Katherine E.

AU - Sebastin, Monisha

AU - Odgis, Jacqueline A.

AU - Abhyankar, Avinash

AU - Brown, Kaitlyn

AU - Di Biase, Miranda

AU - Gallagher, Katie M.

AU - Guha, Saurav

AU - Ioele, Nicolette

AU - Okur, Volkan

AU - Ramos, Michelle A.

AU - Rodriguez, Jessica E.

AU - Rehman, Atteeq U.

AU - Thomas-Wilson, Amanda

AU - Edelmann, Lisa

AU - Zinberg, Randi E.

AU - Diaz, George A.

AU - Greally, John M.

AU - Jobanputra, Vaidehi

AU - Suckiel, Sabrina A.

AU - Horowitz, Carol R.

AU - Wasserstein, Melissa P.

AU - Kenny, Eimear E.

AU - Gelb, Bruce D.

PY - 2023/9

Y1 - 2023/9

N2 - 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.

AB - 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.

KW - Clinical genetics

KW - Genetic testing

KW - Genomic medicine

KW - Genomics

KW - Molecular diagnostic test

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DO - 10.1016/j.gim.2023.100880

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AN - SCOPUS:85162085800

SN - 1098-3600

VL - 25

JO - Genetics in Medicine

JF - Genetics in Medicine

IS - 9

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ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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