Lessons learned from rapid exome sequencing for 575 critically ill patients across the broad spectrum of rare disease.

Autor:	Marouane A; Department of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands.; Department of Neonatology, Radboud University Medical Center, Radboud Institute for Health Sciences, Amalia Children's Hospital, Nijmegen, Netherlands., Neveling K; Department of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands.; Research Institute for Medical Innovation, Radboud University Medical Center, Nijmegen, Netherlands., Deden AC; Department of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands., van den Heuvel S; Department of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands., Zafeiropoulou D; Department of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands., Castelein S; Department of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands., van de Veerdonk F; Department of Internal Medicine, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, Netherlands., Koolen DA; Department of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands., Simons A; Department of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands., Rodenburg R; Department of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands., Westra D; Research Institute for Medical Innovation, Radboud University Medical Center, Nijmegen, Netherlands., Mensenkamp AR; Department of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands., de Leeuw N; Department of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands., Ligtenberg M; Department of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands., Matthijsse R; Department of Neonatology, Radboud University Medical Center, Radboud Institute for Health Sciences, Amalia Children's Hospital, Nijmegen, Netherlands., Pfundt R; Department of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands., Kamsteeg EJ; Department of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands., Brunner HG; Department of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands., Gilissen C; Department of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands., Feenstra I; Department of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands., de Boode WP; Department of Neonatology, Radboud University Medical Center, Radboud Institute for Health Sciences, Amalia Children's Hospital, Nijmegen, Netherlands., Yntema HG; Department of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands., van Zelst-Stams WAG; Department of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands., Nelen M; Department of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands., Vissers LELM; Department of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands.; Research Institute for Medical Innovation, Radboud University Medical Center, Nijmegen, Netherlands.
Jazyk:	angličtina
Zdroj:	Frontiers in genetics [Front Genet] 2024 Jan 08; Vol. 14, pp. 1304520. Date of Electronic Publication: 2024 Jan 08 (Print Publication: 2023).
DOI:	10.3389/fgene.2023.1304520
Abstrakt:	Introduction: Rapid exome sequencing (rES) has become the first-choice genetic test for critically ill patients, mostly neonates, young infants, or fetuses in prenatal care, in time-sensitive situations and when it is expected that the genetic test result may guide clinical decision making. The implementation of rES has revolutionized medicine by enabling timely identification of genetic causes for various rare diseases. The utilization of rES has increasingly been recognized as an essential diagnostic tool for the identification of complex and undiagnosed genetic disorders. Methods: We conducted a retrospective evaluation of our experiences with rES performed on 575 critically ill patients from various age groups (prenatal to adulthood), over a four-year period (2016-2019). These patients presented with a wide spectrum of rare diseases, including but not limited to neurological disorders, severe combined immune deficiency, and cancer. Results: During the study period, there was a significant increase in rES referrals, with a rise from a total of two referrals in Q1-2016 to 10 referrals per week in Q4-2019. The median turnaround time (TAT) decreased from 17 to 11 days in the period 2016-2019, with an overall median TAT of 11 days (IQR 8-15 days). The overall diagnostic yield for this cohort was 30.4%, and did not significantly differ between the different age groups (e.g. adults 22.2% vs children 31.0%; p -value 0.35). However, variability in yield was observed between clinical entities: craniofacial anomalies yielded 58.3%, while for three clinical entities (severe combined immune deficiency, aneurysm, and hypogonadotropic hypogonadism) no diagnoses were obtained. Discussion: Importantly, whereas clinical significance is often only attributed to a conclusive diagnosis, we also observed impact on clinical decision-making for individuals in whom no genetic diagnosis was established. Hence, our experience shows that rES has an important role for patients of all ages and across the broad spectrum of rare diseases to impact clinical outcomes. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Marouane, Neveling, Deden, van den Heuvel, Zafeiropoulou, Castelein, van de Veerdonk, Koolen, Simons, Rodenburg, Westra, Mensenkamp, de Leeuw, Ligtenberg, Matthijsse, Pfundt, Kamsteeg, Brunner, Gilissen, Feenstra, de Boode, Yntema, van Zelst-Stams, Nelen and Vissers.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu