Purpose: Few studies have systematically analyzed the structure and content of laboratory exome sequencing reports from the same patient.Methods: We merged 8 variants from patients into "normal"... Show morePurpose: Few studies have systematically analyzed the structure and content of laboratory exome sequencing reports from the same patient.Methods: We merged 8 variants from patients into "normal" exomes to create virtual patient-parent trios. We provided laboratories worldwide with the data and patient phenotype information (developmental delay, dysmorphic features, and cardiac hypertrophy). Laboratories analyzed the data and issued a diagnostic exome report. Reports were scored using a coding matrix developed from existing guidelines.Results: In total, 41 laboratories representing 17 countries issued reports. Reporting of quality control statistics and technical information was poor (46.3%). Although 75.6% of the reports clearly stated the classification of all reported variants, few reports listed extensive evidence supporting variant classification. Only 53.1% of laboratories that reported unsolicited or secondary findings gave advice regarding health-related follow-up and 20.5% gave advice regarding cascade testing for relatives. Of the 147 variants reported, 105 (71.4%) were classified in agreement with classifications based on American College of Medical Genetics and Genomics/Association for Molecular Pathology and Association for Clinical Genomic Science guidelines. Concordance was higher for known pathogenic variants (86.3%) than for novel unpublished variants (56.8%).Conclusion: The considerable variability identified in the components that laboratories included in their reports and their classification of variants suggests that existing guidelines are not being used consistently with significant implications for patient care. (C) 2022 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved. Show less
Vears, D.F.; Elferink, M.; Kriek, M.; Borry, P.; Gassen, K.L. van 2020
Purpose Existing research suggests that while some laboratories report variants of uncertain significance, unsolicited findings (UF), and/or secondary findings (SF) when performing exome sequencing... Show morePurpose Existing research suggests that while some laboratories report variants of uncertain significance, unsolicited findings (UF), and/or secondary findings (SF) when performing exome sequencing, others do not. Methods To investigate reporting differences, we created virtual patient-parent trio data by merging variants from patients into "normal" exomes. We invited laboratories worldwide to analyze the data along with patient phenotype information (developmental delay, dysmorphic features, and cardiac hypertrophy). Laboratories issued a diagnostic exome report and completed questionnaires to explain their rationale for reporting (or not reporting) each of the eight variants integrated. Results Of the 39 laboratories that completed the questionnaire, 30 reported the HDAC8 variant, which was a partial cause of the patient's primary phenotype, and 26 reported the BICD2 variant, which explained another phenotypic component. Lack of reporting was often due to using a filter or a targeted gene panel that excluded the variant, or because they did not consider the variant to be responsible for the phenotype. There was considerable variation in reporting variants associated with the cardiac phenotype (MYBPC3 and PLN) and reporting UF/SF also varied widely. Conclusion This high degree of variability has significant impact on whether causative variants are identified, with important implications for patient care. Show less
Dondorp, W.; Wert, G. de; Bombard, Y.; Bianchi, D.W.; Bergmann, C.; Borry, P.; ... ; American Soc Human Genetics 2015
The participation of minors in biobank research can offer great benefits for science and health care. However, as minors are a vulnerable population they are also in need of adequate protective... Show moreThe participation of minors in biobank research can offer great benefits for science and health care. However, as minors are a vulnerable population they are also in need of adequate protective measures when they are enrolled in research. Research using biobanked biological samples from children poses additional ethical issues to those raised by research using adult biobanks. For example, small children have only limited capacity, if any, to understand the meaning and implications of the research and to give a documented agreement to it. Older minors are gradually acquiring this capacity. We describe principles for good practice related to the inclusion of minors in biobank research, focusing on issues related to benefits and subsidiarity, consent, proportionality and return of results. Some of these issues are currently heavily debated, and we conclude by providing principles for good practice for policy makers of biobanks, researchers and anyone involved in dealing with stored tissue samples from children. Actual implementation of the principles will vary according to different jurisdictions. Show less
Hastings, R.; Wert, G. de; Fowler, B.; Krawczak, M.; Vermeulen, E.; Bakker, E.; ... ; Cornel, M.C. 2012
An increasing number of private companies are now offering direct-to-consumer (DTC) genetic testing services. Although a lot of attention has been devoted to the regulatory framework of DTC genetic... Show moreAn increasing number of private companies are now offering direct-to-consumer (DTC) genetic testing services. Although a lot of attention has been devoted to the regulatory framework of DTC genetic testing services in the USA, only limited information about the regulatory framework in Europe is available. We will report on the situation with regard to the national legislation on DTC genetic testing in seven European countries (Belgium, the Netherlands, Switzerland, Portugal, France, Germany, the United Kingdom). The paper will address whether these countries have legislation that specifically address the issue of DTC genetic testing or have relevant laws that is pertinent to the regulatory control of these services in their countries. The findings show that France, Germany, Portugal and Switzerland have specific legislation that defines that genetic tests can only be carried out by a medical doctor after the provision of sufficient information concerning the nature, meaning and consequences of the genetic test and after the consent of the person concerned. In the Netherlands, some DTC genetic tests could fall under legislation that provides the Minister the right to refuse to provide a license to operate if a test is scientifically unsound, not in accordance with the professional medical practice standards or if the expected benefit is not in balance with the (potential) health risks. Belgium and the United Kingdom allow the provision of DTC genetic tests.European Journal of Human Genetics advance online publication, 25 January 2012; doi:10.1038/ejhg.2011.278. Show less
Forzano, F.; Borry, P.; Cambon-Thomsen, A.; Hodgson, S.V.; Tibben, A.; Vries, P. de; ... ; Cornel, M. 2010
A few months ago, the controversial debate on connection between genetic variants and antisocial behaviour gained renewed prominence after the sentence of an Italian judge who decided to further... Show moreA few months ago, the controversial debate on connection between genetic variants and antisocial behaviour gained renewed prominence after the sentence of an Italian judge who decided to further reduce the prison sentence of a person convicted of murder by 1 year - from 9 to 8 years - because he was found to be a carrier of a few genetic variants thought to be associated with a predisposition to aggressiveness. We discuss the social implication of this view, the lack of evidence of the clinical utility of this test, and in particular the risks of offering susceptibility testing in the context of legal proceedings. European Journal of Human Genetics (2010) 18, 519-521; doi:10.1038/ejhg.2010.31; published online 10 March 2010 Show less
