title: Unsolved challenges in pediatric whole-exome sequencing: A literature analysis.
abstract: Whole-exome sequencing (WES) has been instrumental in the discovery of novel genes and mechanisms causing Mendelian diseases. While this technology is now being successfully applied in a number of clinics, particularly to diagnose patients with rare diseases, it also raises a number of ethical, legal and social issues. In order to identify what challenges were directly foreseen by technology users, we performed a systematic review of the literature. In this paper, we focus on recent publications related to the use of WES in the pediatric context and analyze the most prominent challenges raised by technology users. This is particularly relevant considering that a) most patients currently undergoing testing using WES to identify the genetic basis for rare diseases are children and b) their lack of capacity to consent for themselves makes them a vulnerable population and generates the need for specific ethical, legal and regulatory procedures. We identified key challenges that related to four main categories: (1) intake; (2) sequence production and analysis; (3) reporting of results and counseling considerations and (4) collaborative data interpretation and data sharing. We then contextualize these challenges in light of the recent recommendations and guidelines, published by professional societies that have significant potential to impact the field.
authors.affiliation: a Department of Human Genetics , Centre of Genomics and Policy, McGill University , Montreal , QC , Canada.|b UMR 1027, Inserm, Université Toulouse III - Paul Sabatier , Toulouse , France.
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Bertier
authors.affiliation: a Department of Human Genetics , Centre of Genomics and Policy, McGill University , Montreal , QC , Canada.
authors.forename: Karine
authors.initials: K
authors.lastname: Sénécal
authors.affiliation: c Department of Public Health and Primary Care , Leuven Institute for Human Genomics and Society , KU Leuven , Leuven , Belgium and.
authors.forename: Pascal
authors.initials: P
authors.lastname: Borry
authors.affiliation: c Department of Public Health and Primary Care , Leuven Institute for Human Genomics and Society , KU Leuven , Leuven , Belgium and.|d Center for Biomedical Ethics and Law , KU Leuven , Leuven , Belgium.
authors.forename: Danya F
authors.initials: DF
authors.lastname: Vears
mesh_terms: D002648:Child; D059472:Exome / Q000235:genetics*; D005820:Genetic Testing / Q000941:ethics*; D023281:Genomics / Q000941:ethics; D006801:Humans; D010372:Pediatrics / Q000941:ethics; D035583:Rare Diseases / Q000175:diagnosis / Q000235:genetics; D017422:Sequence Analysis, DNA / Q000941:ethics*
keywords: Whole-exome sequencing; children; ethical; legal and social issues; pediatrics; technology users; unsolved challenges