BACKGROUND: Genetic testing rapidly penetrates into all medical specialties and medical students must acquire skills in this area. However, many of them consider it difficult. Furthermore, many find these topics less appealing and not connected to their future specialization in different fields of clinical medicine. Student-centred strategies such as problem-based learning, gamification and the use of real data can increase the appeal of a difficult topic such as genetic testing, a field at the crossroads of genetics, molecular biology and bioinformatics. METHODS: We designed an electronic teaching application which students registered in the undergraduate Medical Biology course can access online. A study was carried out to assess the influence of implementation of the new method. We performed pretest/posttest evaluation and analyzed the results using the sign test with median values. We also collected students' personal comments. RESULTS: The newly developed interactive application simulates the process of molecular genetic diagnostics of a hereditary disorder in a family. Thirteen tasks guide students through clinical and laboratory steps needed to reach the final diagnosis. Genetics and genomics are fields strongly dependent on electronic databases and computer-based data analysis tools. The tasks employ publicly available internet bioinformatic resources used routinely in medical genetics departments worldwide. Authenticity is assured by the use of modified and de-identified clinical and laboratory data from real families analyzed in our previous research projects. Each task contains links to databases and data processing tools needed to solve the task, and an answer box. If the entered answer is correct, the system allows the user to proceed to the next task. The solving of consecutive tasks arranged into a single narrative resembles a computer game, making the concept appealing. There was a statistically significant improvement of knowledge and skills after the practical class, and most comments on the application were positive. A demo version is available at https://medbio.lf2.cuni.cz/demo_m/ . Full version is available on request from the authors. CONCLUSIONS: Our concept proved to be appealing to the students and effective in teaching medical molecular genetics. It can be modified for training in the use of electronic information resources in other medical specialties.

• MeSH
• genetické nemoci vrozené diagnóza   MeSH
• genetické testování * MeSH
• lékařská genetika výchova   MeSH
• lidé MeSH
• molekulární medicína výchova   MeSH
• počítačem řízená výuka * MeSH
• problémově orientovaná výuka MeSH
• studium lékařství pregraduální metody   MeSH
• uživatelské rozhraní počítače MeSH
• videohry MeSH
• výpočetní biologie výchova   MeSH
• vyučování MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• hodnotící studie MeSH

The importance of gonadal mosaicism in families with apparently de novo mutations is being increasingly recognized. We report on two affected brothers initially suggestive of X-linked or autosomal recessive inheritance. Malan syndrome due to shared NFIX variants was diagnosed in the brothers using exome sequencing. The boys shared the same paternal but not maternal haplotype around NFIX, and deep amplicon sequencing showed ~7% of the variant in paternal sperm but not in paternal blood and saliva. We performed review of previous cases of gonadal mosaicism, which suggests that the phenomenon is not uncommon. Gonadal mosaicism is often not accompanied by somatic mosaicism in tissues routinely used for testing, and if both types of mosaicism are present, the frequency of the variant in sperm is often higher than in somatic cells. In families with shared apparently de novo variants without evidence of parental somatic mosaicism, the transmitting parent may be determined through haplotyping of exome variants. Gonadal mosaicism has important consequences for recurrence risks and should be considered in genetic counseling in families with de novo variants.

• MeSH
• dítě MeSH
• gonády patologie   MeSH
• lidé MeSH
• mladý dospělý MeSH
• mnohočetné abnormality genetika   MeSH
• mozaicismus * MeSH
• mutace genetika   MeSH
• předškolní dítě MeSH
• rodokmen MeSH
• sekvence aminokyselin MeSH
• sekvence nukleotidů MeSH
• sourozenci * MeSH
• syndrom MeSH
• těhotenství MeSH
• transkripční faktory NFI chemie   genetika   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH