Reducing diagnostic turnaround times of exome sequencing for families requiring timely diagnoses Aur  elie Bourchany a, b , Christel Thauvin-Robinet b, c , Daphn  e Lehalle b, c , Ange-Line Bruel b , Alice Masurel-Paulet b, c , Nolwenn Jean b, c , Sophie Nambot b, c , Marjorie Willems d , Laetitia Lambert e , Salima El Chehadeh-Djebbar f , Elise Schaefer f , Aur  elia Jaquette g , Judith St-Onge b , Charlotte Poe b , Thibaud Jouan b , Martin Chevarin b , Patrick Callier b, h , Anne-Laure Mosca-Boidron b, h , Nicole Laurent i , Mathilde Lefebvre b , Fr  ed  eric Huet a, b , Nada Houcinat b, c ,S  ebastien Moutton b, c , Christophe Philippe b, h , Fr  ed  eric Tran-Mau-Them b, h , Antonio Vitobello h , Paul Kuentz b , Yannis Duffourd b , Jean-Baptiste Rivi  ere b, h , Julien Thevenon b, c, *, 1 , Laurence Faivre b, c, **, 1 a D epartement de P ediatrie 1, H^ opital d’Enfants, CHU Dijon et Universit e de Bourgogne, Dijon, France b Equipe G en etique des Anomalies du D eveloppement, INSERM UMR1231, Universit e de Bourgogne-Franche Comt e, Dijon, France c Centre de G en etique et Centre de R ef erence Anomalies du D eveloppement et Syndromes Malformatifs, FHU TRANSLAD, H^ opital d’Enfants, CHU Dijon et Universit e de Bourgogne, Dijon, France d D epartement de G en etique Clinique, CHRU de Montpellier, H^ opital Arnaud de Villeneuve, Montpellier, France e Unit e Fonctionnelle de G en etique Clinique, Service de M edecine N eonatale, Maternit eR egionale Universitaire, Nancy, France f Service de G en etique M edicale, H^ opital de Hautepierre, Strasbourg, France g Centre de G en etique, H^ opital de la Piti e-Salp etri ere, Paris, France h Laboratoire de G en etique chromosomique mol eculaire, Plateau technique de Biologie, CHU, Dijon, France i Laboratoire d'anatomopathologie, Plateau technique de Biologie, CHU, Dijon, France article info Article history: Received 22 March 2017 Received in revised form 27 June 2017 Accepted 10 August 2017 Available online xxx Keywords: Exome sequencing Diagnostic turnaround time Undiagnosed genetic conditions abstract Background and objective: Whole-exome sequencing (WES) has now entered medical practice with powerful applications in the diagnosis of rare Mendelian disorders. Although the usefulness and cost- effectiveness of WES have been widely demonstrated, it is essential to reduce the diagnostic turn- around time to make WES a first-line procedure. Since 2011, the automation of laboratory procedures and advances in sequencing chemistry have made it possible to carry out diagnostic whole genome sequencing from the blood sample to molecular diagnosis of suspected genetic disorders within 50 h. Taking advantage of these advances, the main objective of the study was to improve turnaround times for sequencing results. Methods: WES was proposed to 29 patients with severe undiagnosed disorders with developmental abnormalities and faced with medical situations requiring rapid diagnosis. Each family gave consent. The extracted DNA was sequenced on a NextSeq500 (Illumina) instrument. Data were analyzed following standard procedures. Variants were interpreted using in-house software. Each rare variant affecting protein sequences with clinical relevance was tested for familial segregation. Results: The diagnostic rate was 45% (13/29), with a mean turnaround time of 40 days from reception of the specimen to delivery of results to the referring physician. Besides permitting genetic counseling, the rapid diagnosis for positive families led to two pre-natal diagnoses and two inclusions in clinical trials. Abbreviations: WES, Whole Exome Sequencing; WGS, Whole Genome Sequencing; ID, Intellectual Deficiency. * Corresponding author. Centre de G en etique, Centre de R ef erence Maladies Rares “Anomalies du D eveloppement et Syndromes Malformatifs”,H^ opital d'Enfants, 14 rue Gaffarel, 21079, Dijon Cedex, France. ** Corresponding author. Centre de G en etique, Centre de R ef erence Maladies Rares “Anomalies du D eveloppement et Syndromes Malformatifs”,H^ opital d'Enfants, 14 rue Gaffarel, 21079, Dijon Cedex, France. E-mail addresses: jthevenon@chu-grenoble.fr (J. Thevenon), laurence.faivre@chu-dijon.fr (L. Faivre). 1 These authors equally contributed to the work. Contents lists available at ScienceDirect European Journal of Medical Genetics journal homepage: http://www.elsevier.com/locate/ejmg http://dx.doi.org/10.1016/j.ejmg.2017.08.011 1769-7212/© 2017 Published by Elsevier Masson SAS. European Journal of Medical Genetics xxx (2017) 1e10 Please cite this article in press as: Bourchany, A., et al., Reducing diagnostic turnaround times of exome sequencing for families requiring timely diagnoses, European Journal of Medical Genetics (2017), http://dx.doi.org/10.1016/j.ejmg.2017.08.011