Clinical application of fetal genome-wide sequencing during pregnancy: position statement of the Canadian College of Medical Geneticists.

Autor:	Lazier J; Department of Genetics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada jlazier@cheo.on.ca., Hartley T; Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Ontario, Canada., Brock JA; Departments of Pathology & Laboratory Medicine and Obstetrics & Gynaecology, IWK Health Centre, Halifax, Nova Scotia, Canada., Caluseriu O; Medical Genetics Clinic, University of Alberta, Edmonton, Alberta, Canada., Chitayat D; The Prenatal Diagnosis and Medical Genetics Program, Department of Obstetrics and Gynecology, University of Toronto, Toronto, Ontario, Canada.; Division of Clinical and Metabolic Genetics, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada., Laberge AM; Service de Génétique Médicale, CHU Sainte-Justine and Département de Pédiatrie, Université de Montréal, Montréal, Quebec, Canada., Langlois S; Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada., Lauzon J; Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.; Alberta Children's Hospital Research Institute for Child and Maternal Health, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada., Nelson TN; Department of Pathology and Laboratory Medicine, BC Children's Hospital and BC Women's Hospital Vancouver, Vancouver, British Columbia, Canada.; Department of Pathology and Laboratory Medicine, The University of British Columbia, Vancouver, British Columbia, Canada., Parboosingh J; Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.; Alberta Children's Hospital Research Institute for Child and Maternal Health, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada., Stavropoulos DJ; Genome Diagnostics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada., Boycott K; Department of Genetics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.; Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Ontario, Canada., Armour CM; Department of Genetics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.; Prenatal Screening Ontario (PSO), Better Outcomes Registry & Network (BORN) Ontario, Ottawa, Ontario, Canada.
Jazyk:	angličtina
Zdroj:	Journal of medical genetics [J Med Genet] 2022 Oct; Vol. 59 (10), pp. 931-937. Date of Electronic Publication: 2021 Sep 20.
DOI:	10.1136/jmedgenet-2021-107897
Abstrakt:	Purpose and Scope: The aim of this position statement is to provide recommendations for Canadian healthcare professionals regarding the use of genome-wide sequencing (GWS) in the context of diagnostic testing of the fetus during pregnancy. This statement was developed to facilitate clinical translation of GWS as a prenatal diagnostic test and the development of best practices in Canada, but the applicability of this document is broader and aims to help professionals in other healthcare systems. Methods of Statement Development: A multidisciplinary group was assembled to review existing literature on fetal GWS for genetic diagnosis in the context of suspected monogenic diseases and to make recommendations relevant to the Canadian context. The statement was circulated for comments to the Canadian College of Medical Geneticists (CCMG) membership-at-large and, following incorporation of feedback, approved by the CCMG Board of Directors on 19 February 2021. Results and Conclusions: The use of prenatal GWS is indicated for the investigation of multiple fetal anomalies. Its use in the context of isolated fetal anomaly should be guided by available resources and current evidence, which is continually changing. During pregnancy, GWS should be ordered by, or in collaboration with, a medical geneticist. It should be used following detailed phenotyping to interrogate known disease genes, preferably using a trio approach, following detailed fetal phenotyping. Testing should be done with an overall aim to help in the management of the pregnancy, delivery and postnatal care. It should be guided by personal utility of the test for the pregnant person and clinical utility for pregnancy and birth management, as outlined herein. Genetic counselling is crucial in making the parental decision an informed decision. Chromosomal microarray analysis should be completed in parallel or prior to GWS and should be preceded by Quantitative Fluorescent PCR (QF-PCR) for detection of common aneuploidies. In normal circumstances, only pathogenic and likely pathogenic variants with a high likelihood of being associated with the identified fetal anomalies should be reported. Reporting of secondary findings, defined as purposeful analysis of variants in a set of medically actionable genes, should not, by default, be performed in the prenatal context. Laboratories should only report incidental findings that reveal risk of a significant Mendelian condition during infancy and childhood. Should a laboratory have a policy for reporting incidental findings in medically actionable adult-onset conditions, they should only be reported with explicit opt-in consent signed by the tested individuals. Genetic counselling is crucial in disclosing the test results and the implications the results may have for the fetus. It should be emphasised that negative results do not rule out a genetic diagnosis nor guarantee a good prognosis. Postnatal phenotyping and reanalysis of existing data should be considered. Families should be given the opportunity to participate in research studies as appropriate. These recommendations will be routinely re-evaluated as knowledge of the diagnostic and clinical utility of fetal GWS during pregnancy improves. Competing Interests: Competing interests: TN: spouse employed by Illumina. (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu