Current State of Compulsory Basic and Clinical Courses in Genetics for Medical Students at Medical Faculties in Balkan Countries With Slavic Languages

Introduction: In this study we aimed to perform the first research on the current state of compulsory basic and clinical courses in genetics for medical students offered at medical faculties in six Balkan countries with Slavic languages (Bosnia and Herzegovina, Croatia, Montenegro, North Macedonia, Serbia, and Slovenia).Materials and Methods: The study was conducted from June to September 2021. One representative from each country was invited to collect and interpret the data for all medical faculties in their respective country. All representatives filled a questionnaire, which consisted of two sets of questions. The first set of questions was factual and contained specific questions about medical faculties and design of compulsory courses, whereas the second set of questions was more subjective and inquired the opinion of the representatives about mandatory education in clinical medical genetics in their countries and internationally. In addition, full course syllabi were analysed for course aims, learning outcomes, course content, methods for student evaluation and literature.Results: Detailed analysis was performed for a total of 22 medical faculties in Bosnia and Herzegovina (6), Croatia (4), Montenegro (1), North Macedonia (3), Serbia (6), and Slovenia (2). All but the two medical faculties in Slovenia offer either compulsory courses in basic education in human genetics (16 faculties/courses) or clinical education in medical genetics (3 faculties/courses). On the other hand, only the medical faculty in Montenegro offers both types of education, including one course in basic education in human genetics and one in clinical education in medical genetics. Most of the basic courses in human genetics have similar aims, learning outcomes and content. Conversely, clinical courses in medical genetics are similar concerning study year position, number of contact hours, ECTS (European Credit Transfer and Accumulation System) and contents, but vary considerably regarding aims, learning outcomes, ratio of types of classes, teaching methods and student evaluation.Conclusion: Our results emphasise the need for future collaboration in reaching a consensus on medical genetics education in Balkan countries with Slavic languages. Further research warrants the analysis of performance of basic courses, as well as introducing clinical courses in medical genetics to higher years of study across Balkan countries.

Management of biobanking for medical genetics research

Biobanking is one of the most important elements of the modern infrastructure for biomedical research. Organization of a biobank on the basis of the N. P. Bochkov Medical Genetics Research Center provides a centralized infrastructure for preparing biomaterial for research. Biobank has the format of a research equipment sharing center and works with two types of unique biomaterials from patients with genetic diseases: blood/blood components and vital cells of various tissue origin. The storage facility of the Biobank is equipped with low-temperature (-80° C) and cryostorage (-196° C) systems. Identification and search of samples is carried out using a bar-coding system and is implemented through the information interface of the biobank, which is integrated into the general database of patients at the Medical Genetics Research Center. Information on biomaterial samples is presented in periodically updated catalogs on the page of equipment sharing center “Biobank”. Biobank collection is available to internal and external users.

Genomics and predictive medicine

Progress in understanding of structural and functional human genome organization and deciphering primary DNA sequence in human cells allowed for hitherto unreachable new capabilities of medical genetics in identifying the causes and mechanisms of inherited and inborn pathology. Implementation of genetics into medicine is progressively advancing along with improvement of molecular analysis of genome. Knowledge of genome and its functions allows to provide more accurate diagnosis, predict, to a considerable extent, the presence of genetic predisposition of a person to pathology, and to assess the chances for developing one or another disease. This approach became the basis for a new area of medical genetics named predictive medicine. The progress of predictive medicine refl ects success in tremendous upgrowth of molecular genetic methods and new capabilities of studying structure and functions of genome. Within less than 15 years after deciphering genome, medical genetics has travelled a long way from a single gene analysis to whole genome studies, from screening of genetic associations to systems genetics of multifactorial diseases, from translational to high-precision genetics, and from genetic passport idea to electronic genetic health records. The development of a genetic passport, prognostic genetic testing, and genomic chart of reproductive health is especially relevant for current practical medicine.

Exome Sequencing Highlights a Potential Role for Concealed Cardiomyopathies in Youthful Sudden Cardiac Death

Background: Sudden cardiac arrest (SCA) and sudden unexplained death (SUD) are feared sequelae of many genetic heart diseases. In rare circumstances, pathogenic variants in cardiomyopathy-susceptibility genes may result in electrical instability leading to SCA/SUD before any structural manifestations of underlying cardiomyopathy are evident. Methods: Collectively, 38 unexplained SCA survivors (21 males; mean age at SCA 26.4±13.1 years), 68 autopsy-inconclusive SUD cases (49 males; mean age at death 20.4±9.0 years) without disease-causative variants in the channelopathy genes, and 973 ostensibly healthy controls were included. Following exome sequencing, ultrarare (minor allele frequency ≤0.00005 in any ethnic group within Genome Aggregation Database [gnomAD, n=141 456 individuals]) nonsynonymous variants identified in 24 ClinGen adjudicated definitive/strong evidence cardiomyopathy-susceptibility genes were analyzed. Eligible variants were adjudicated as pathogenic, likely pathogenic, or variant of uncertain significance in accordance with current American College of Medical Genetics and Genomics guidelines. Results: Overall, 7 out of 38 (18.4%) SCA survivors and 14 out of 68 (20.5%) autopsy-inconclusive, channelopathic-negative SUD cases had at least one pathogenic/likely pathogenic or a variant of uncertain significance nonsynonymous variant within a strong evidence, cardiomyopathy-susceptibility gene. Following American College of Medical Genetics and Genomics criterion variant adjudication, a pathogenic or likely pathogenic variant was identified in 3 out of 38 (7.9%; P =0.05) SCA survivors and 8 out of 68 (11.8%; P =0.0002) autopsy-inconclusive SUD cases compared to 20 out of 973 (2.1%) European controls. Interestingly, the yield of pathogenic/likely pathogenic variants was significantly greater in autopsy-inconclusive SUD cases with documented interstitial fibrosis (4/11, 36%) compared with only 4 out of 57 (7%, P <0.02) SUD cases without ventricular fibrosis. Conclusion: Our data further supports the inclusion of strongevidence cardiomyopathy-susceptibility genes on the genetic testing panels used to evaluate unexplained SCA survivors and autopsy-inconclusive/negative SUD decedents. However, to avoid diagnostic miscues, the careful interpretation of genetic test results in patients without overt phenotypes is vital.