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Observational Study
. 2022 Jul;141(7):1269-1278.
doi: 10.1007/s00439-021-02358-0. Epub 2021 Sep 8.

Diagnostic yield of clinical exome sequencing as a first-tier genetic test for the diagnosis of genetic disorders in pediatric patients: results from a referral center study

Jean-Philippe Mergnac  1   2 , Arnaud Wiedemann  1   3   4 , Céline Chery  1   4   5 , Jean-Marie Ravel  1 , Farès Namour  1   4   5 , Jean-Louis Guéant  1   4   5 , François Feillet  1   2   4 , Abderrahim Oussalah  6   7   8
Affiliations
Observational Study

Diagnostic yield of clinical exome sequencing as a first-tier genetic test for the diagnosis of genetic disorders in pediatric patients: results from a referral center study

Jean-Philippe Mergnac et al. Hum Genet. 2022 Jul.

Abstract

The emergence of next-generation sequencing enabled a cost-effective and straightforward diagnostic approach to genetic disorders using clinical exome sequencing (CES) panels. We performed a retrospective observational study to assess the diagnostic yield of CES as a first-tier genetic test in 128 consecutive pediatric patients addressed to a referral center in the North-East of France for a suspected genetic disorder, mainly an inborn error of metabolism between January 2016 and August 2020. CES was performed using the TruSight One (4811 genes) or the TruSight One expanded (6699 genes) panel on an Illumina sequencing platform. The median age was 6.5 years (IQR 2.0-12.0) with 43% of males (55/128), and the median disease duration was 7 months (IQR 1-47). In the whole analysis, the CES diagnostic yield was 55% (70/128). The median test-to-report time was 5 months (IQR 4-7). According to CES indications, the CES diagnostic yields were 81% (21/26) for hyperlipidemia, 75% (6/8) for osteogenesis imperfecta, 64% (25/39) for metabolic disorders, 39% (10/26) for neurological disorders, and 28% (8/29) for the subgroup of patients with miscellaneous conditions. Our results demonstrate the usefulness of a CES-based diagnosis as a first-tier genetic test to establish a molecular diagnosis in pediatric patients with a suspected genetic disorder with a median test-to-report time of 5 months. It highlights the importance of a close interaction between the pediatrician with expertise in genetic disorders and the molecular medicine physician to optimize both CES indication and interpretation. Diagnostic yield of clinical exome sequencing (CES) as a first-tier genetic test for diagnosing genetic disorders in 128 consecutive pediatric patients referred to a reference center in the North-East of France for a suspected genetic disorder, mainly an inborn error of metabolism between January 2016 and August 2020. The CES diagnostic yields are reported in the whole population and patients' subgroups (hyperlipidemia, osteogenesis imperfecta, metabolic diseases, neurological disorders, miscellaneous conditions) (Icons made by Flaticon, flaticon.com; CC-BY-3.0).

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References

    1. Adams DR, Eng CM (2018) Next-generation sequencing to diagnose suspected genetic disorders. N Engl J Med 379:1353–1362. https://doi.org/10.1056/NEJMra1711801 - DOI
    1. Amberger JS, Bocchini CA, Scott AF, Hamosh A (2019) OMIM.org: leveraging knowledge across phenotype-gene relationships. Nucleic Acids Res 47:D1038–D1043. https://doi.org/10.1093/nar/gky1151 - DOI
    1. Anikster Y, Haack TB, Vilboux T, Pode-Shakked B, Thony B, Shen N, Guarani V, Meissner T, Mayatepek E, Trefz FK, Marek-Yagel D, Martinez A, Huttlin EL, Paulo JA, Berutti R, Benoist JF, Imbard A, Dorboz I, Heimer G, Landau Y, Ziv-Strasser L, Malicdan MCV, Gemperle-Britschgi C, Cremer K, Engels H, Meili D, Keller I, Bruggmann R, Strom TM, Meitinger T, Mullikin JC, Schwartz G, Ben-Zeev B, Gahl WA, Harper JW, Blau N, Hoffmann GF, Prokisch H, Opladen T, Schiff M (2017) Biallelic mutations in DNAJC12 cause hyperphenylalaninemia, dystonia, and intellectual disability. Am J Hum Genet 100:257–266. https://doi.org/10.1016/j.ajhg.2017.01.002 - DOI - PMC
    1. Australian Genomics Health Alliance Acute Care F, Lunke S, Eggers S, Wilson M, Patel C, Barnett CP, Pinner J, Sandaradura SA, Buckley MF, Krzesinski EI, de Silva MG, Brett GR, Boggs K, Mowat D, Kirk EP, Ades LC, Akesson LS, Amor DJ, Ayres S, Baxendale A, Borrie S, Bray A, Brown NJ, Chan CY, Chong B, Cliffe C, Delatycki MB, Edwards M, Elakis G, Fahey MC, Fennell A, Fowles L, Gallacher L, Higgins M, Howell KB, Hunt L, Hunter MF, Jones KJ, King S, Kumble S, Lang S, Le Moing M, Ma A, Phelan D, Quinn MCJ, Richards A, Richmond CM, Riseley J, Rodgers J, Sachdev R, Sadedin S, Schlapbach LJ, Smith J, Springer A, Tan NB, Tan TY, Temple SL, Theda C, Vasudevan A, White SM, Yeung A, Zhu Y, Martyn M, Best S, Roscioli T, Christodoulou J, Stark Z (2020) Feasibility of ultra-rapid exome sequencing in critically ill infants and children with suspected monogenic conditions in the Australian public health care system. JAMA 323:2503–2511. https://doi.org/10.1001/jama.2020.7671 - DOI
    1. Chardon JW, Smith AC, Woulfe J, Pena E, Rakhra K, Dennie C, Beaulieu C, Huang L, Schwartzentruber J, Hawkins C, Harms MB, Dojeiji S, Zhang M, Consortium FC, Majewski J, Bulman DE, Boycott KM, Dyment DA (2015) LIMS2 mutations are associated with a novel muscular dystrophy, severe cardiomyopathy and triangular tongues. Clin Genet 88: 558–564. https://doi.org/10.1111/cge.12561

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