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Large-scale next-generation sequencing (NGS) germline testing is technically feasible today, but variant interpretation represents a major bottleneck in analysis workflows. This includes extensive variant prioritization, annotation, and time-consuming evidence curation. The scale of the interpretation problem is massive, and variants of uncertain significance (VUSs) are a challenge to personalized medicine. This challenge is further compounded by the complexity and heterogeneity of the standards used to describe genetic variants and the associated phenotypes when searching for relevant information to support clinical decision making. To address this, all five Swiss academic institutions for Medical Genetics joined forces with the Swiss Institute of Bioinformatics (SIB) to create SwissGenVar as a user-friendly nationwide repository and sharing platform for genetic variant data generated during routine diagnostic procedures and research sequencing projects. Its aim is to provide a protected environment for expert evidence sharing about individual variants to harmonize and upscale their significance interpretation at the clinical grade according to international standards. To corroborate the clinical assessment, the variant-related data will be combined with consented high-quality clinical information. Broader visibility will be achieved by interfacing with international databases, thus supporting global initiatives in personalized healthcare.

The use of genome-wide sequencing (GWS) in paediatrics has added complexity to informed consent (IC) and pretest counselling because of the vast number and interpretation of potential findings, and their implications. However, empirical data from continental Europe on these issues remains limited. This study therefore aimed to explore the experiences and views of medical geneticists working with children in Germany and Switzerland regarding the challenges of obtaining valid IC in paediatric GWS. Qualitative interviews with 20 medical geneticists were analysed employing reflexive thematic analysis. In the interviews, many medical geneticists questioned the validity of parents’ IC due to the enormous amount of relevant information given and the variety and complexity of the possible test outcomes. Key barriers identified included familial implications, administrative challenges and struggles with non-directiveness. Medical geneticists’ suggestions for improvement included increasing the number of genetics professionals and better information material, which is crucial as GWS becomes a diagnostic standard in the early care pathways of children. An adjustment of aspirations from still existing ideal of traditional fully IC to appropriate IC seems to be needed. Such a more realistic and ethically sound adaptation of the requirements for IC can lead to better ‘informedness’ and improve the validity of the consent. This might also help reduce the moral distress for the medical geneticists involved.

Large-scale next-generation sequencing (NGS) germline testing is technically feasible today, but variant interpretation represents a major bottleneck in analysis workflows including the extensive variant prioritization, annotation, and time-consuming evidence curation. The scale of the interpretation problem is massive, and variants of uncertain significance (VUS) are a challenge to personalized medicine. This challenge is further compounded by the complexity and heterogeneity of standards used to describe genetic variants and associated phenotypes when searching for relevant information to inform clinical decision-making. For this purpose, all five Swiss academic Medical Genetics Institutions joined forces with the Swiss Institute of Bioinformatics (SIB) to create SwissGenVar as a user-friendly nationwide repository and sharing platform for genetic variant data generated during routine diagnostic procedures and research sequencing projects. Its objective is to provide a protected environment for expert evidence sharing about individual variants to harmonize and up-scale their significance interpretation at clinical grade following international standards. To corroborate the clinical assessment, the variant-related data are combined with consented high-quality clinical information. Broader visibility will be gained by interfacing with international databases, thus supporting global initiatives in personalized health care.

Genetische Beratung Die Medizinische Genetik hat sich von einem Randgebiet zu einer zentralen klinischen Disziplin in der Medizin entwickelt. Der enorme Wissenszuwachs der letzten Jahre zu Phänotypen und Genotypen, zu Ätiologie und Verlauf seltener und häufiger Krankheiten wirkt sich auf alle Fachbereiche der klinischen Medizin aus. Viele haben jedoch nur eine vage Vorstellung, was eine genetische Beratung beinhaltet. = Génétique Bien que marginale à ses débuts, la médecine génétique s’est développée en une discipline clinique essentielle. L’énorme croissance des connaissances de ces dernières années en ce qui concerne les phénotypes et génotypes ainsi que l’étiologie et l’évolution de maladies rares et fréquentes entraîne des répercussions sur toutes les spécialités de la médecine. Cependant, beaucoup n’ont qu’une vague idée de ce que devrait contenir un conseil génétique.

Arts syndrome or phosphoribosyl-pyrophosphate-synthetase-1 (PRPS1) deficiency is caused by loss-of-function mutations in the PRPS1 gene (Xq22.3). PRPS1 is an initial and essential step for the synthesis of the nucleotides of purines, pyrimidines, and nicotinamide. Classically, affected males present with sensorineural hearing loss, optic atrophy, muscular hypotonia, developmental impairment, and recurrent severe respiratory infections early in life. Treatment of a 3-year old boy with S-adenosylmethionine (SAM) replenished erythrocyte purine nucleotides of adenosine and guanosine, while SAM and nicotinamide riboside co-therapy further improved his clinical phenotype as well as T-cell survival and function.

Background The use of genome-wide sequencing in pediatric medicine and research is growing exponentially. While this has many potential benefits, the normative and empirical literature has highlighted various ethical issues. There have not been, however, any systematic reviews of these issues. The aim of this systematic review is to determine systematically the spectrum of ethical issues that is raised for stakeholders in in pediatric genome-wide sequencing. Methods A systematic review in PubMed and Google Books (publications in English or German between 2004 and 2021) was conducted. Further references were identified via reference screening. Data were analyzed and synthesized using qualitative content analysis. Ethical issues were defined as arising when a relevant normative principle is not adequately considered or when two principles come into conflict. Results Our literature search retrieved 3175 publications of which 143 were included in the analysis. Together these mentioned 106 ethical issues in pediatric genome-wide sequencing, categorized into five themes along the pediatric genome-wide sequencing lifecycle. Most ethical issues identified in relation to genome-wide sequencing typically reflect ethical issues that arise in general genetic testing, but they are often amplified by the increased quantity of data obtained, and associated uncertainties. The most frequently discussed ethical aspects concern the issue of unsolicited findings. Conclusion Concentration of the debate on unsolicited findings risks overlooking other ethical challenges. An overarching difficulty presents the terminological confusion: both with regard to both the test procedure/ the scope of analysis, as well as with the topic of unsolicited findings. It is important that the genetics and ethics communities together with other medical professions involved work jointly on specific case related guidelines to grant the maximum benefit for the care of the children, while preventing patient ha

Mit den rasanten technologischen Entwicklungen im medizinisch-genomischen Bereich und dem damit verbundenen exponentiellen Kenntniszuwachs hat der Bedarf an genetischer Expertise in praktisch allen medizinischen Disziplinen zugenommen. Die Schweizerische Gesellschaft für Medizinische Genetik (SGMG) sieht sich als Fachgesellschaft und Vertreterin einer transversalen medizinischen Disziplin besonders geeignet, die gegebene Situation zu evaluieren und zukünftige Konzepte zu entwickeln und zu begleiten.

Neue Methoden der Genomanalyse erlauben es, im Blut einer schwangeren Frau festzustellen, ob krankhafte genetische Abweichungen beim Embryo vorliegen. Damit wird es vergleichsweise einfach, schon in einer frühen Phase der Schwangerschaft Aussagen über Chromosomen-Anomalien und weitere genetische Merkmale des Ungeborenen zu erhalten. Die seit wenigen Jahren erhältlichen nicht-invasiven Pränataltests (NIPT) sind gemäss ersten Erfahrungen sehr verlässlich, zudem entfallen die Risiken für den Fötus, die mit einer invasiven Untersuchung wie z.B. der Fruchtwasserpunktion einhergehen. Mit einer breiteren Anwendung der NIPT und mit der zunehmenden Anzahl von Krankheitsrisiken, die damit untersucht werden können, sind offene Fragen verbunden. Welche Tests sind sinnvoll? Wie gehen die Betroffenen mit den Informationen um? Wie wird die Beratung sichergestellt? In der interdisziplinären Studie werden Chancen und Risiken von vorgeburtlichen genetischen Untersuchungen abgeschätzt. Die Studie zeigt auf, wie sich die neuen Tests auf die Zukunft der pränatalen Diagnostik auswirken könnten, analysiert gesellschaftliche, ethische, rechtliche und ökonomische Fragen und formuliert Empfehlungen.

Neue Methoden der Genomanalyse erlauben es, im Blut einer schwangeren Frau festzustellen, ob krankhafte genetische Abweichungen beim Embryo vorliegen. Damit wird es vergleichsweise einfach, schon in einer frühen Phase der Schwangerschaft Aussagen über Chromosomen-Anomalien und weitere genetische Merkmale des Ungeborenen zu erhalten. Die seit wenigen Jahren erhältlichen nicht-invasiven Pränataltests (NIPT) sind gemäss ersten Erfahrungen sehr verlässlich, zudem entfallen die Risiken für den Fötus, die mit einer invasiven Untersuchung wie z.B. der Fruchtwasserpunktion einhergehen. Mit einer breiteren Anwendung der NIPT und mit der zunehmenden Anzahl von Krankheitsrisiken, die damit untersucht werden können, sind offene Fragen verbunden. Welche Tests sind sinnvoll? Wie gehen die Betroffenen mit den Informationen um? Wie wird die Beratung sichergestellt? In der interdisziplinären Studie werden Chancen und Risiken von vorgeburtlichen genetischen Untersuchungen abgeschätzt. Die Studie zeigt auf, wie sich die neuen Tests auf die Zukunft der pränatalen Diagnostik auswirken könnten, analysiert gesellschaftliche, ethische, rechtliche und ökonomische Fragen und formuliert Empfehlungen.