16p11.2 600 kb Duplications confer risk for typical and atypical Rolandic epilepsy

Rolandic epilepsy (RE) is the most common idiopathic focal childhood epilepsy. Its molecular basis is largely unknown and a complex genetic etiology is assumed in the majority of affected individuals. The present study tested whether six large recurrent copy number variants at 1q21, 15q11.2, 15q13.3, 16p11.2, 16p13.11 and 22q11.2 previously associated with neurodevelopmental disorders also increase risk of RE. Our association analyses revealed a significant excess of the 600 kb genomic duplication at the 16p11.2 locus (chr16: 29.5-30.1 Mb) in 393 unrelated patients with typical (n = 339) and atypical (ARE; n = 54) RE compared with the prevalence in 65 046 European population controls (5/393 cases versus 32/65 046 controls; Fisher's exact test P = 2.83 × 10−6, odds ratio = 26.2, 95% confidence interval: 7.9-68.2). In contrast, the 16p11.2 duplication was not detected in 1738 European epilepsy patients with either temporal lobe epilepsy (n = 330) and genetic generalized epilepsies (n = 1408), suggesting a selective enrichment of the 16p11.2 duplication in idiopathic focal childhood epilepsies (Fisher's exact test P = 2.1 × 10−4). In a subsequent screen among children carrying the 16p11.2 600 kb rearrangement we identified three patients with RE-spectrum epilepsies in 117 duplication carriers (2.6%) but none in 202 carriers of the reciprocal deletion. Our results suggest that the 16p11.2 duplication represents a significant genetic risk factor for typical and atypical R

Evaluation of presumably disease causing SCN1A variants in a cohort of common epilepsy syndromes

Objective: The SCN1A gene, coding for the voltage-gated Na+ channel alpha subunit NaV1.1, is the clinically most relevant epilepsy gene. With the advent of high-throughput next-generation sequencing, clinical laboratories are generating an ever-increasing catalogue of SCN1A variants. Variants are more likely to be classified as pathogenic if they have already been identified previously in a patient with epilepsy. Here, we critically re-evaluate the pathogenicity of this class of variants in a cohort of patients with common epilepsy syndromes and subsequently ask whether a significant fraction of benign variants have been misclassified as pathogenic. Methods: We screened a discovery cohort of 448 patients with a broad range of common genetic epilepsies and 734 controls for previously reported SCN1A mutations that were assumed to be disease causing. We re-evaluated the evidence for pathogenicity of the identified variants using in silico predictions, segregation, original reports, available functional data and assessment of allele frequencies in healthy individuals as well as in a follow up cohort of 777 patients. Results and Interpretation: We identified 8 known missense mutations, previously reported as path

Ringvorlesung Gender Medizin an den medizinischen Universitäten Innsbruck und Wien: Ein Lehrformat im Vergleich

Introduction: Diversity-specific differences in health, illness and access to a health system have meanwhile been studied well. Educating medical students offers good leverage for broadening this knowledge within the medical professions. One approach is to use elective subjects.Project Description: The goal of this work is to compare the lecture series on Gender Medicine at the Medical Universities of Innsbruck and Vienna.Results: The cornerstones of both of these lecture series (topics that vary per semester, various lecturers speaking on a predefined cross-cutting topic) are similar. Various approaches prevail for the target groups and the lecturers as well as the question of credit for external students. Both universities tackle different medical disciplines each semester while concentrating on gender-specific questions.Teacher evaluation in Innsbruck as well as the feedback from the students in Vienna show that the lecture series have a positive impact on how the various diversity categories influence health and illness.Discussion: Ensuring that a particular leitmotif runs through the various lectures of a lecture series entails increased planning and organizational work. On the other hand, various medical disciplines and their perspectives can be presented in a lecture series.Conclusion: The lecture series are embedded in overall strategies at the two universities. Ensuring the sustainability of the integration of Gender Medicine as a cross-cutting topic in medical education is, however, only possible when combined with other efforts.Einleitung: Diversitätsspezifische Unterschiede in Gesundheit, Krankheit und Zugang zum Gesundheitssystem sind mittlerweile gut untersucht. Um dieses Wissen innerhalb der medizinischen Berufsgruppen zu verbreitern, ist die Ausbildung der Medizinstudent*innen ein wichtiger Hebel. Ein Ansatzpunkt ist die Nutzung von Wahlfächern.Projektbeschreibung: Ziel ist die vergleichende Darstellung der Ringvorlesungen zu Gender Medizin an den Medizinischen Universitäten Innsbruck und Wien.Ergebnisse: Die Grundpfeiler der Lehrveranstaltung (semesterweise wechselnde Themen, verschiedene Vortragende zu einem vorab definierten, quer zu den Disziplinen liegenden Thema) sind ähnlich. Sowohl bei Zielgruppen und Vortragenden als auch bei der Frage der Anrechnung für Externe gibt es verschiedene Zugänge. Inhaltlich bearbeiten beide semesterweise wechselnde medizinische Fachgebiete mit dem Schwerpunkt auf geschlechtsspezifischen Fragestellungen. Sowohl die in Innsbruck vorliegende Evaluation durch Lehrende als auch das Feedback der Studierenden in Wien zeigen, dass die Ringvorlesungen die Auseinandersetzung mit dem Einfluss verschiedener Diversitätskategorien auf Gesundheit und Krankheit positiv beeinflussen.Diskussion: Die Sicherstellung eines 'roten-Fadens' in den unterschiedlichen Vorträgen einer zusammenhängenden Ringvorlesung ist mit einem erhöhten Planungs- und Organisationsaufwand verbunden. Dafür können in einer Ringvorlesung verschiedene Fachdisziplinen und ihre Perspektiven zu Wort kommen.Schlussfolgerung: Die Ringvorlesungen sind eingebettet in Gesamtstrategien an den jeweiligen Universitäten. Eine nachhaltige Integration von Gender Medizin als Querschnittsthema der Lehre ist jedoch nur gemeinsam mit anderen Maßnahmen erfolgsversprechend